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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 3  |  Page : 363-369

Clinical audit of anticoagulant therapy with pregnancy


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Azhar University (Assiut), Assiut, Egypt
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Minia University, Minia, Egypt

Date of Submission27-Jun-2020
Date of Decision30-Jul-2020
Date of Acceptance13-Aug-2020
Date of Web Publication30-Oct-2020

Correspondence Address:
Asmaa M Mahmoud
Faculty of Medicine, Minia University, Minia 11651
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_96_20

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  Abstract 


Background and aim Anticoagulant use in pregnant women should be paid great attention in both the period of pregnancy and the postpartum period. Risks and benefits to the mother and fetus should be balanced in the choice of anticoagulant therapy. Clinical audit can be defined as the process of assessment through the use of evidence-based criteria and/or the outcome of care by comparison with others. In the current study, the aim was to audit the anticoagulant therapy usage in pregnancy and compared it with the chosen international standards (RCOG standards).
Patients and methods The study was done at Gynecology and Obstetrics Department of Minia General Hospital, Egypt, on 300 pregnant women on anticoagulant therapy.
Results Regarding the percent of patients following the international guidelines among the 300 studied cases on anticoagulant therapy, 174 (58%) cases agreed with RCOG guidelines and 126 (42%) did not agree with RCOG guidelines.
Conclusion The use of anticoagulant in pregnancy must be balanced according to the benefit and the risks of use.

Keywords: anticoagulant therapy, clinical audit, pregnant women, RCOG standards


How to cite this article:
El-Rasheedy MI, Mohammed AH, Mahmoud AM. Clinical audit of anticoagulant therapy with pregnancy. Al-Azhar Assiut Med J 2020;18:363-9

How to cite this URL:
El-Rasheedy MI, Mohammed AH, Mahmoud AM. Clinical audit of anticoagulant therapy with pregnancy. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Dec 4];18:363-9. Available from: http://www.azmj.eg.net/text.asp?2020/18/3/363/299585




  Introduction Top


Thromboembolic disorders can be considered a fatal problem in pregnancy. Anticoagulant therapy plays an important role in both treatment and prevention. Warfarin is the best drug to use but carries the risk of bleeding in mothers and fetus, especially in the late pregnancy and delivery. Moreover, the risks of embryopathy from warfarin in early pregnancy cannot be excluded. Parenteral heparin has the advantage of the inability to cross the placental barrier but still can be a cause of bleeding problems in pregnancy, and its long-term use still carries the problems of maternal bone demineralization [1].

So, no anticoagulant therapy can be used during pregnancy and be free of risk, so all management policies must depend on an estimate of risk–benefit ratio in individual patients [2].

Low-molecular-weight heparin (LMWH) can be used in pregnancy for prophylactic and therapeutic anticoagulation. Owing to its improved bioavailability, the longer half‐life, and the reduced risks of heparin‐induced thrombocytopenia and osteoporosis, LMWH use is a more convenient proposition than unfractionated heparin. Therapeutic doses during pregnancy can be indicated in patient who present with acute venous thromboembolism (VTE), for those carrying a high risk of recurrent thromboembolism, and patients with a major cardiac disease such as artificial heart valves [3].

The rationale for LMWH use in VTE treatment in pregnancy can be based on previous studies which have shown that therapeutic LMWH is as safe and effective as unfractionated heparin in the acute management of VTE. However, in pregnancy, owing to the fetal effects of warfarin, secondary prophylaxis is done with heparin or LMWH for the duration of pregnancy [4].

The anticoagulant and thrombolytic use in pregnancy is a very important consideration, as pregnancy is associated with a fivefold increase in VTE risk, with the risk rising to 20-fold or more throughout the puerperium. The risk further increases if thrombophilia is associated. The risk of VTE can persist till 12 weeks of postpartum [5].

The aim of this work was to compare and audit the use of anticoagulant therapy in pregnancy according to RCOG guidelines.


  Patients and methods Top


Prospective data were collected from pregnant women on anticoagulant therapy in the Department of Obstetrics and Gynecology of Minia General Hospital, Egypt, to identify women who received anticoagulant therapy with pregnancy. A total of 300 pregnant women were included in this study. The study protocol was approved by the ethics committee of Faculty of Medicine, Al Azhar University Council.

Inclusion criteria

Pregnant women on anticoagulant therapy with an age range from 18 to 35 years were included.

Exclusion criteria

Pregnant women not on anticoagulant therapy and those with multiple pregnancies were included.

All cases were subjected to the following:

Detailed history taking, including personal history and demographic data (name, age, and residence), obstetric history (gestational age, parity, delivery, detailed menstrual history recurrent miscarriage, and obstetrical problems), patient complaint, history of present illness, past history of any medical disease or surgical history, family history of similar or related condition, social history, and dose, duration, and indication of anticoagulant therapy use.

General and systemic examination, including pulse, blood pressure, temperature, complexion, cardiac disease, respiratory problems, gastrointestinal tract system, urinary system, lymphatic system, and endocrine diseases.

Ultrasonography examination

to asses fetal viability and weight

to asses amniotic fluid

to assess placental site.

Statistical analysis

Data were coded and entered to Statistical Package for Social Science (USA), version 8 to detect a statically significant difference.


  Results Top


The study was done at Gynecology and Obstetrics Department of Minia General Hospital, Egypt, and the target population was all patients who were admitted to the hospital during a period of 6 months from November 2019 to April 2020. In the present study, we aimed to audit the use of anticoagulant therapy in pregnancy to ascertain compliance with agreed upon guidelines. A total of 300 pregnant women were included in this study.

Patients’ demographic and clinical characteristics

[Table 1] shows the patients’ demographic and clinical characteristics.
Table 1 Patients demographic and clinical characteristics

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Indication of administration of anticoagulant therapy for studied cases

In our study, 64 patients who were on anticoagulant therapy had recurrent pregnancy loss, including owing to antiphospholipid syndrome in 44 (14.7%) patients and owing to thrombophilia in 20 (6.7%) patients, and this agrees with RCOG guidelines ([Table 2]).
Table 2 Risk factors for administration of anticoagulant therapy for studied cases

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Unexplained recurrent pregnancy lost

A total of 73 (24.3%) patients had unexplained recurrent pregnancy loss, but this did not agree with RCOG guidelines ([Table 3]).
Table 3 Recurrent pregnancy loss (unexplained recurrent pregnancy lost) (total N=73)

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Abortion history among studied cases

A total of 41 (13.7%) patients had abortion; 23 (7.7%) patients had abortion one time and 18 (6.0%) patients had abortions for two times, and this did not agree with RCOG guidelines ([Table 4]).
Table 4 Abortion history among studied cases (total N=41)

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Intrauterine growth restriction and oligohydramnios history among studied cases

A total of 22 patients (7.3%) had a history of intrauterine growth restriction and oligohydramnios, and this agreed with RCOG guidelines ([Table 5]).
Table 5 Intrauterine growth restriction and oligohydramnios history among studied cases (total N=22)

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Deep venous thrombosis history among studied cases

A total of 46 (15.3%) patients had a history of deep venous thrombosis, and this agreed with RCOG guidelines ([Table 6]).
Table 6 Precious baby among studied cases (total N=15)

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Precious baby among studied cases

A total of 15 (5%) patients had a history of precious baby, and this did not agree with RCOG guidelines ([Table 7]).
Table 7 Deep venous thrombosis history among studied cases (total N=46)

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Recurrent abortion due to thrombophilia history among studied cases

Recurrent pregnancy loss owing to thrombophilia was seen in 20 (6.7%) patients, and this agreed with RCOG guidelines ([Table 8]).
Table 8 Recurrent abortion owing to antiphospholipid syndrome history among studied cases (total N=44)

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Autoimmune diseases history among studied cases

A total of 12 (4%) patients had a history of autoimmune diseases, and this agreed with RCOG guidelines ([Table 9]).
Table 9 Recurrent abortion owing to thrombophilia history among studied cases (total N=20)

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Cardiac valve replacement history among studied cases

A total of 19 (6.3%) patients had cardiac valve replacement history, and this agreed with RCOG guidelines ([Table 10]).
Table 10 Autoimmune diseases history among studied cases (total N=12)

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Prolonged recumbence history as fractures among studied cases

A total of eight (2.7%) patients had a history of fracture, and this agreed with RCOG guidelines ([Table 11]).
Table 11 Cardiac valve replacement history among studied cases (total N=19)

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Percent of following international guidelines among studied cases

Regarding the percent of patients following international guidelines among 300 studied cases on anticoagulant therapy, 174 (58%) cases agreed with RCOG guidelines and 126 (42%) did not agree with RCOG guidelines ([Table 12] and [Table 13]).
Table 12 Prolonged recumbency history such as fractures among studied cases (total N=8)

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Table 13 Percent of patients following international guidelines among the studied cases (total N=300)

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  Discussion Top


Clinical audit can be defined as the assessment of the process using evidence-based criteria and/or the outcome of care by comparison with others. It aimed to support the national and the local quality and to improve interventions through reauditing, so it can assess the effect of those interventions [6].

Clinical audit is ‘a quality improvement process that seeks to improve the patient care and outcomes through systematic review of care against explicit criteria and the implementation of change’ [7].

The study was done at Gynecology and Obstetrics Department at Minia General Hospital, Egypt, and the target population was all patients who were admitted to the hospital during a period of 6 months from November 2019 to April 2020. In the present study, we aimed to audit the use of anticoagulant therapy in pregnancy and compared it with the chosen international standards (RCOG standards).

The mean age of women participating in the study was ∼28 years.

The current data showed that ∼29.3% of our study population was living in urban areas and ∼70.7% in rural areas.

In our study, anticoagulant was used in 300 pregnant women. A total of 73 (24.3%) patients had unexplained recurrent pregnancy loss, and this disagreed with RCOG guidelines.

Women with unexplained recurrent miscarriage have an excellent prognosis for future pregnancy outcome without pharmacological intervention if received supportive care alone in early pregnancy assessment unit.

A significant number of recurrent miscarriage cases remain unexplained despite the detailed investigation, so these women must be reassured that the prognosis for the future pregnancy is successful with supportive care alone in nearly 75%.

However, the prognosis may worsen with increasing maternal age and the number of miscarriages. Aspirin alone or in combination with heparin can be prescribed for women with unexplained recurrent miscarriage, aiming to improving the pregnancy outcome. Two randomized controlled trials reported that neither of these interventions can improve the live birth rate among women with unexplained recurrent miscarriage; however, both studies included a significant number of women with just two previous miscarriages (40 and 57% of the study population, respectively) [8].

In another prospective randomized study of the administration of enoxaparin and aspirin to unexplained recurrent miscarriage patients done by Dolitzky et al. [9], 104 women were randomized as 40 mg enoxaparin group and 100 mg aspirin group, and when fetal cardiac activity was seen, prophylaxis was started and live birth rate was 81.5% in enoxaparin group and 84% in aspirin group.

Fawzy et al. [10] achieved a live birth rate of 81% using enoxaparin 20 mg a day in women with more than or equal to three fetal losses when compared with control group with a live birth rate of 48%.

Moreover, in our study, there were 64 patients with recurrent pregnancy loss due to antiphospholipid syndrome [44 patients (14.7%)] and thrombophilia (20 patients) and were on anticoagulant therapy, and this agrees with RCOG guidelines.

Pregnant women with antiphospholipid syndrome should use low-dose aspirin plus heparin to prevent further miscarriage.

A meta-analysis of 76 randomized controlled trials examined the outcomes of different treatments including aspirin, steroids, intravenous globulin, and heparin used to improve pregnancy outcome in women with recurrent miscarriage associated with antiphospholipid antibodies. This meta-analysis reported that aspirin in addition to unfractionated heparin is the only treatment, which leads to a significant increase in the live birth rate among women with antiphospholipid syndrome, as it significantly reduces the miscarriage rate by 54% (aspirin plus unfractionated heparin compared with aspirin alone) [11].

Heparin therapy during pregnancy may improve the live birth rate of women with second-trimester miscarriage associated with inherited thrombophilia. Cohort studies have suggested that heparin therapy may improve the live birth rate for these women [12].

Moreover, in our study, 41 (13.7%) patients had abortion history; 23 (7.7%) patients had abortion one time and 18 (6.0%) patients had abortion two times, and were on anticoagulant therapy, and this disagrees with RCOG guidelines.

Moreover, in our study, 22 (7.3%) patients had intrauterine growth restriction and oligohydramnios and were on anticoagulant therapy, and this agrees with RCOG guidelines.

Antithrombotic therapy has been used to improve outcome in women at risk of placental dysfunction. A systematic review of five studies involving 484 women, four of which compared heparin (either alone or with dipyridamole) with no treatment, found that heparin reduced the incidence of SGA neonates from 25 to 9% and also reduced the incidence of pre-eclampsia [13].

Moreover, in our study, 46 (15.3%) patients had a history of deep venous thrombosis and were on anticoagulant therapy, and this agrees with RCOG guidelines.

Antenatal thromboprophylaxis for those with previous VTE should begin as early in pregnancy, as most of VTE occurs antenatal with an equal distribution throughout gestation. Several studies have found that 40–50% of antenatal VTE occurred before 15 weeks of gestation, so, there is a need for risk assessment before pregnancy [14].

Moreover, in our study, 19 (6.3%) patients had pregnancy with cardiac valve replacement history and were on anticoagulant therapy, and this agree with RCOG guidelines.

Mechanical heart valves require a lifelong anticoagulation. Warfarin produces risks of the fetus teratogenesis, intracerebral bleeding, and fetal loss. Heparin does not cross the placenta but has a higher risk of maternal thrombosis. They need to continue full anticoagulation throughout the pregnancy. When heparin is used, low-dose aspirin (75 mg/day) should be added. Heparin dose and compliance should be monitored with anti-Xa level. All women should thus be thoroughly counseled before pregnancy regarding these risks. A plan should be made to cover delivery and anticoagulation postnatally. In the case of bleeding or the need for urgent delivery in a fully anticoagulated patient, warfarin may be reversed with recombinant human factor VIIa/fresh frozen plasma and vitamin K, and heparin with protamine [15].

There were 12 (4%) patients who were pregnant with autoimmune diseases history and were on anticoagulant therapy, and this agrees with RCOG guidelines, which found a strong association between the autoimmune diseases and the obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome, and autoimmune thyroiditis, which resulted in miscarriage and preterm birth [16].

There were eight (2.7%) patients who were pregnant with a history of prolonged recumbence such as fracture and were on anticoagulant therapy, and this agrees with RCOG guidelines.The risk of VTE is increased fivefold to tenfold in pregnancy. The hypercoagulability of pregnancy persists for several weeks after delivery, and the greatest risk for VTE is in the early postpartum period. The recent decline in maternal deaths from VTE can be attributed to the use of thromboprophylaxis in high-risk women.

There are multiple risk factors that increase the risk of VTE. Several guidelines have been proposed as a risk assessment score. The appropriate use of prophylaxis depends on identification of patients who are at high risk of VTE, and risk assessment is recommended early during pregnancy and also in the postpartum period.

Risk factors include previous VTE, family history of VTE, hereditary thrombophilia, antiphospholipid syndrome, medical comorbidities, significant pregnancy complications, cesarean delivery, prolonged antepartum immobilization, and clinical risk factors, such as increased body mass index, age more than 35 years, and parity more than or equal to 3 [17].

There were 15 (5%) patients who were pregnant with precious baby and were on anticoagulant therapy, and this disagrees with RCOG guidelines.


  Conclusion Top


Women requiring anticoagulation need careful attention throughout pregnancy and the postpartum period. Risks and benefits to the mother and fetus should be balanced in the choice of anticoagulant therapy, degree of monitoring, and therapeutic target. Future research should investigate different approaches and combinations of anticoagulant agents in pregnancy. Development of anticoagulant agents that are homogeneous, efficacious, safe to the fetus, and not affected by physiological perturbations of pregnancy will have a tremendous effect on the outcomes of pregnancy in women who require anticoagulation.

Recommendations

We recommend in our study to follow the RCOG guidelines for VTE prophylaxis during pregnancy and postpartum period and to stop the misuse of anticoagulant in nonindicated circumstances.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e691S–e736S.  Back to cited text no. 1
    
2.
Bennett SA, Bagot CN, Appiah A, Johns J, Ross J, Roberts LN et al. Women with unexplained recurrent pregnancy loss do not have evidence of an underlying prothrombotic state: experience with calibrated automated thrombography and rotational thromboelastometry. Thromb Res 2014; 133:892–899.  Back to cited text no. 2
    
3.
Rowan JA, McLintock C, Taylor RS, North RA. Prophylactic and therapeutic enoxaparin during pregnancy: indications, outcomes and monitoring. Aust N Z J Obstet Gynaecol 2003; 43:123–128.  Back to cited text no. 3
    
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Chan WS, Rey E, Kent NE, Chan WS, Kent NE; VTE in Pregnancy Guideline Working Group, et al... Venous thromboembolism and antithrombotic therapy in pregnancy. J ObstetGynaecol Can 2014; 36:527–553.  Back to cited text no. 4
    
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Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ. 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. 5
    
6.
Department of Health/Healthcare Quality Improvement Partnership/National Advisory Group on Clinical Audit and Enquiries (NAGCAE). Detection and Management of Outliers for National Clinical Audits. 2011.  Back to cited text no. 6
    
7.
Copeland G. A practical handbook for clinical audit. Guidance published by the Clinical Governance Support Team. 2005. Available at: www. cgsupport. nhs.uk/ downloads/ Practical_ Clinical_ Audit_Handbook_v1_1.pdf. [Accessed February 2012].  Back to cited text no. 7
    
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Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M et al. Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010; 115:4162–4167.  Back to cited text no. 8
    
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Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H. A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. Fertil Steril 2006; 86:362–326.  Back to cited text no. 9
    
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Fawzy M, Shokeir T, Tatongy ML, Warda O, El-Refaiey AA, Mosbah A. Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study. Arch Gynecol Obstet 2008; 278:33–38.  Back to cited text no. 10
    
11.
Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005; 2:CD002859.  Back to cited text no. 11
    
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Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J; LIVE-ENOX Investigators. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3:227–229.  Back to cited text no. 12
    
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Dodd JM, McLeod A, Windrim R, Kingdom J. Anthithrombotic therapy for improving maternal and infant health outcomes in women considered at risk of placental dysfunction. Cochrane Database Syst Rev 2010; 6:C D006780.  Back to cited text no. 13
    
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Blanco-Molina A, Trujillo-Santos J, Criado J, Lopez L, Lecumberri R, Gutierrez R et al. Venous thromboembolism during pregnancy or postpartum: findings from the RIETE Registry. Thromb Haemost 2007; 97:186–190.  Back to cited text no. 14
    
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RCOG Good Practice. Cardiac Disease and Pregnancy; (Good Practice No. 13). Royal College of Obstetricians and Gynaecologists; 2011.  Back to cited text no. 15
    
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Gomes V, Mesquita A, Capela C. Autoimmune diseases and pregnancy: analysis of a series of cases. BMC Res Notes 2015; 8:216.  Back to cited text no. 16
    
17.
Bain E, Wilson A, Tooher R, Gates S, Davies LJ, Middleton P. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane DatabSyst Rev 2014; 2:CD001689.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13]



 

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