THROMBO-EMBOLIC DISORDERS





15.1 Thrombophilia and Inherited Clotting Disorders

15.2 Deep Vein Thrombosis

15.3 Pulmonary Embolism

15.4 Thromboprophylaxis




15.1 Thrombophilia and Inherited Clotting Disorders






Incidence

Approximately 10% of the general population have an inherited thrombophilia

Risk for Childbearing

Variable or High Risk – depending upon type of disorder




EXPLANATION OF CONDITION


The term thrombophilia refers to disorders of the haemostatic system that result in an increased risk of thrombosis. It includes inherited and acquired risk factors.


Inherited



  • Factor V Leiden (FVL)
  • Prothrombin 20210
  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin deficiency

Acquired



  • Antiphospholipid syndrome (see Section 11.4)

Complex



  • Raised factor VIII levels
  • Hyperhomocysteinaemia

COMPLICATIONS



  • The relative risk of VTE varies with the nature of the thrombophilia but is greatest for antithrombin deficiency and antiphospholipid syndrome
  • Thrombophilias existing in combination act synergistically, with a resulting risk greater than would be expected for the sum of the individual factors
  • There is increased risk for gestational venous thrombosis, recurrent miscarriage and late pregnancy complications

NON-PREGNANCY TREATMENT AND CARE


Women with a previous history of thrombosis should be screened for thrombophilia prior to pregnancy.


Other relative indications for testing include:



  • Individuals with a first-degree family history of VTE or known thrombophilia who are planning pregnancy or intending to undergo a procedure or course of treatment that would greatly increase their risk of thrombosis:

    • orthopaedic surgery
    • hormone replacement therapy
    • combined oral contraceptive pill
    • invasive vascular procedures

  • Previous history of unprovoked or minimally provoked thrombosis.
  • Children or young adults with thrombosis
  • Women with a history of unexpected pregnancy complications should be tested for antiphospholipid antibodies (see Section 11.4):

    • three or more early miscarriages
    • late fetal loss
    • stillbirth
    • early or severe pre-eclampsia
    • placental abruption
    • poor fetal growth

  • Young patients with unexplained arterial thrombosis should be investigated for antiphospholipid antibodies

PRE-CONCEPTION ISSUES AND CARE


For potential childbearing there are:



  • Increased thrombotic risks
  • Potential associations with:

    • recurrent miscarriage
    • fetal loss
    • placental abruption
    • pre-eclampsia
    • poor fetal growth

Women with thrombophilia should be informed of their diagnosis and its implications. Counselling should be reinforced by written patient information where possible.



  • Advise against using the combined oral contraceptive pill, which acts in synergy with FVL and other thrombophilia to greatly enhance thrombotic risk
  • Precautions for travel should be highlighted and the importance of additional thromboprophylaxis for high-risk situations such as surgery, prolonged immobility and plaster casts should be emphasised
  • Plans for pregnancy should be discussed before conception and should include thromboprophylactic measures and any need for heparin
  • Ideally patients should be placed on a database and issued with a registration card bearing details of their condition and phone numbers for contact
  • Women with previous thrombosis and who are on long-term warfarin should be made aware of the teratogenic risks. They should keep a diary of their menstrual cycle and seek immediate medical advice if they suspect that they are pregnant
  • Anticoagulation should not be interrupted but provision made to ensure that warfarin is stopped and replaced with heparin no later than 6 weeks gestation





Pregnancy Issues

Thrombosis is usually a multi-hit phenomenon, with cumulative risk factors triggering a clinical event.

Pregnancy significantly increases the risk for patients with underlying thrombophilia, due to a combination of various physiological changes including:


  • A further increase in hypercoagulability as pregnancy advances
  • Decreased venous return secondary to compression of the pelvic veins by the gravid uterus
  • Reduced vessel tone with venous pooling

Of those women with previous VTE, those with underlying thrombophilia are more at risk of recurrent thrombosis than those without. The relative risk varies according to the nature of the thrombophilia, with antithrombin deficiency and antiphospholipid syndrome being the highest.

Antiphospholipid syndrome is characterised by the presence of persistent antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in association with clinical complications. In addition to venous and arterial thrombotic events, it is associated with recurrent miscarriages and late fetal loss, as well as complications in advanced pregnancy including pre-eclampsia, stillbirth and IUGR (see Section 11.4). There is also recent focus on the association of inherited thrombophilia with poor pregnancy outcome.

Pregnant women with acquired thrombophilia, and those with inherited thrombophilia and a complex obstetric or thrombosis history, should be managed by a multidisciplinary team which includes a consultant obstetrician and consultant haematologist. Ideally, the women would be seen in a joint obstetric haematology clinic.








Medical Management and Care

All women should undergo an assessment of thrombotic risk in early pregnancy, taking into account their personal and family histories, the nature of their thrombophilia and any additional acquired risk factors, such as age and obesity. Repeat assessments should be made in the second and third trimesters and each time the circumstances and risk factors change. The risks for VTE, thromboprophylaxis and management for the pregnancy should be discussed with the mother.

Thrombophilia and a history of VTE – these mothers should be offered thromboprophylaxis with antenatal low molecular weight heparin (LMWH), and also for at least 6 weeks postpartum1.

Antiphospholipid (Hughes) syndrome – this is associated with a recurrent thrombotic risk of up to 70%2 and therefore women with antiphospholipid syndrome and previous venous thrombosis should receive heparin from the onset of pregnancy until 6 weeks postpartum. If the condition was diagnosed because of recurrent miscarriages, treatment may not be required in the postpartum period. The addition of aspirin has been shown to improve pregnancy outcome in antiphospholipid syndrome patients with a prior history of obstetric complications3,4 (see Section 11.4).

Asymptomatic inherited or acquired thrombophilia – these women may require antenatal or postnatal thromboprophylaxis depending on the specific thrombophilia. Antithrombin deficiency carries a 30% increased risk of thrombosis in pregnancy and these women should always receive heparin in high prophylactic or treatment doses from the onset of pregnancy. Other thrombophilias requiring antenatal prophylaxis include combined defects and homozygous states. Women with protein C and protein S deficiency may need to start heparin antenatally.

Absent thrombophilia but previous VTE – these women should be offered postpartum prophylaxis with LMWH. It may be reasonable not to use antenatal prophylaxis with heparin for a previous single VTE associated with a temporary risk factor that has now resolved1. However, thromboprophylaxis has been advocated if the previous VTE was related to the combined oral contraceptive pill or if additional acquired risk factors are present5. Also, if there is a positive first-degree family history of VTE, recurrent VTE or a history of thrombosis affecting an unusual site LMWH should be offered antenatally and for at least 6 weeks postnatally1.

Midwifery Management and Care


  • The midwife should be a point of contact so that the woman can inform her regarding the onset of pregnancy. This contact should be continued throughout the pregnancy to report any concerns or changes in circumstances which increase the thrombotic risk
  • The woman should be taught correct self-injection technique and educated regarding safe disposal of ‘sharps’
  • Potential side effects of heparin should be discussed:

    • osteoporosis
    • HIT
    • cutaneous allergy

  • Reinforce general antithrombotic advice regarding hydration, mobility, travel and leg care
  • Ensure that TED stockings have been provided, are a good fit and encourage compliance
  • Ensure use of compression stockings where necessary
  • Be aware of and report any signs and symptoms of complications
  • Effective communication with the community midwife and other members of the multidisciplinary team








Labour Issues – as for DVT and PE (see 15.2 and 15.3)








Management and Care – as for DVT and PE (see 15.2 and 15.3)








Postpartum Issues – as for DVT and PE (see 15.2 and 15.3)








Management and Care – as for DVT and PE (see 15.2 and 15.3)




15.2 Deep Vein Thrombosis






Incidence

1 in 1000 in pregnancy1

Risk for Childbearing

High Risk




EXPLANATION OF CONDITION


Deep vein thrombosis (DVT) is the formation of a blood clot or thrombus in a deep vein, partially or completely occluding the flow of blood. It commonly affects the leg veins but can occur elsewhere. In pregnant women, 85% of DVT occurs in the left leg2 due in part to compression of the left iliac vein by the right iliac artery as they cross3.Virchow described the factors that promote venous thrombosis:



  • Reduction of blood flow (stasis)
  • Alteration of the constituents of the blood (hypercoagulability)
  • Abnormalities/damage to the vessel wall

All three elements of this triad are affected by pregnancy. Pressure of the gravid uterus on the inferior vena cava and pelvic veins, an increase in coagulation factors and reduction in natural inhibitors to anticoagulation and decreased venous tone all predispose to venous thrombo-embolism (VTE).


Symptoms of DVT



  • Pain in area of clot
  • Unilateral and occasionally bilateral swelling
  • Redness or discolouration
  • Difficulty weight bearing on the affected leg
  • Low grade pyrexia
  • Lower abdominal pain if the pelvic veins are affected

COMPLICATIONS


Pulmonary Embolus (PE)


This occurs when a fragment of thrombus breaks away, travels through the right side of the heart and lodges in the pulmonary arterial circulation. Approximately 25% of DVT will be complicated by PE if left untreated. The risk is higher with femoral or ileofemoral thrombus than for more distal DVT.


Post-Thrombotic (or Post-Phlebitic) Syndrome


This long-term complication of DVT arises due to damage of venous valves, resulting in incompetence with reflux and backflow of blood. This increases hydrostatic pressure below the damaged area and causes disruption of the more distal valves, which in turn become incompetent. The venous hypertension leads to oedema and hypoxia of the tissues. Symptoms range from mild to severe and include:



  • Pain
  • Oedema
  • Eczematous dermatitis
  • Pruritus
  • Hyperpigmentation
  • Skin ulceration
  • Cellulitis

Post-thrombotic syndrome occurs in 50% of patients following a DVT4–7, with onset of symptoms often several months or even years after the initial event.


NON-PREGNANCY TREATMENT AND CARE


Prompt treatment is necessary to reduce the risk of extension and propagation of the thrombus and to minimise the risk of post-thrombotic syndrome. Urgent referral is therefore required for all patients with a suspected DVT to confirm the diagnosis objectively. Diagnosis is made from a combination of clinical probability score and radiological imaging. Non-invasive techniques, such as Doppler ultrasound, should be used where possible.


Negative D-dimers associated with a low clinical probability score reliably excludes VTE8. D-dimers are breakdown products of cross-linked fibrin and are raised in inflammatory, infective or malignant conditions. They should not be used to aid positive diagnosis of venous thrombosis but have a high negative predictive value in patients whose clinical probability of VTE is low as assessed by a formal scoring system, as in Table 15.2.1.


Table 15.2.1 LVTE Risk Assessment Scale


Reproduced from RCOG (2009) with the permission of the Royal College of Obstetricians and Gynaecologists






















































































RCOG Risk Assessment for Venous Thromboembolism12
Pre-existing Risk Factors Tick score
Previous recurrent VTE
3
Previous VTE – unprovoked or oestrogen related
3
Previous VTE – provoked
2
Family history of VTE
1
Known thrombophilia
2
Medical comorbidities
2
Age (>35 years)
1
Obesity – Score 1 for BMI >30 kg/m2; 2 for BMI >40 kg/m2 (BMI based on booking weight)
1/2 to 2
Parity ≥3
1
Smoker
1
Gross varicose veins
1
Obstetric risk factors Tick score
Pre-eclampsia
1
Dehydration/hyperemesis/OHSS
1
Multiple pregnancy or conceived by Artificial Reproductive Technology
1
Caesarean section in labour
2
Elective caesarean section
1
Mid-cavity or rotational forceps
1
Prolonged labour (>24 hours)
1
PPH (>1 litre or transfusion)
1
Transient risk factors
Current systemic infection
1
Immobility
1
Surgical procedure in pregnancy or ≤6 weeks postpartum
2
TOTAL

There are different opinions regarding D-dimer testing in pregnancy as they are less likely to be negative in pregnancy. For this reason the Royal College of Obstetricians and Gynaecologists (RCOG)9 do not recommend testing whereas the American College of Chest Physicians (ACCP) do recommend testing


Heparin is the initial treatment of choice, because of its fast onset of anticoagulation and evidence for reduced risk of further thrombo-embolic events8. LMWH has a number of advantages over unfractionated heparin, including predictable dose-response and longer half-life enabling once daily administration. In patients with moderate to high clinical probability scores, heparin should be commenced immediately and continued until the diagnosis is excluded by diagnostic imaging10.


Once a DVT has been confirmed, oral anticoagulation is initiated, in non-pregnant patients, and should be overlapped with heparin therapy until the International Normalized Ratio is greater than 2.0 on two consecutive days10.


The recommended duration of anticoagulation following a first episode of DVT is 3–6 months8, but this needs to be continued depending upon on-going presence of risk factors.


PRE-CONCEPTION ISSUES AND CARE


Pregnancy increases the risk of VTE 10-fold, which increases to 25–fold in the puerperium11. Undetected proximal venous thrombosis can increase the risk of premature labour and abruption. Therefore, where possible, women should be encouraged to optimise health prior to undertaking a pregnancy:



  • If overweight, advise on diet and exercise
  • Stop smoking
  • Reduce caffeine and alcohol intake

Warfarin is contraindicated in pregnancy, other than in exceptional circumstances, and women who are on long-term warfarin should be made aware of the teratogenic risks if taken at 6–12 weeks gestation.






Pregnancy Issues

The risk of thrombosis is present from the first trimester until at least 6 weeks postpartum.

All pregnant women should have thrombotic risk assessment at booking, taking into account their personal and family history, the presence of acquired risk factors and any known thrombophilia (see Table 15.2.1). This should be repeated if circumstances change, such as excessive weight gain, immobility or vomiting with dehydration.

Women should be given advice on ways to reduce thrombotic risk:


  • Keep hydrated
  • Remain as active as possible
  • Avoid standing for long periods
  • Elevate feet when sitting
  • Leg care (massage legs gently with oil or cream)
  • Avoid unnecessary, long journeys by aeroplane, bus or car

Women with a past history of venous thrombo-embolic disease must be booked for antenatal care and delivery at a consultant unit.

If a DVT arises for the first time during pregnancy, the care and place of delivery must be transferred to a consultant unit, if not already done so.

An objective confirmation of diagnosis in pregnancy is crucial, as appropriate treatment reduces morbidity and mortality9, but a false diagnosis has implications for:


  • The current pregnancy
  • Subsequent pregnancies
  • Contraceptive choices
  • HRT decisions
  • Family members

D-dimers are less likely to be helpful in excluding the diagnosis because levels increase as pregnancy advances. Where DVT is suspected, non-invasive testing by ultrasound should be performed.

In addition to warfarin embryopathy during the first trimester, the risks continue throughout pregnancy, with neurological complications in later stages and the risk of fetal intracranial haemorrhage during delivery1,13,14. Continued ongoing low molecular weight heparin (LMWH) is the treatment of choice for DVT in pregnancy.








Medical Management and Care

If there is a high index of suspicion then full anticoagulation should be initiated until thrombo-embolic disease is excluded15.


  • If a Doppler ultrasound is negative but signs and symptoms are persistent and highly suggestive of a DVT the investigations should be repeated after 7 days

Venography confers a small radiation risk to the fetus and should be avoided if possible. However, if on balance of risk it is felt that venography is necessary to obtain a diagnosis, then the fetus should be shielded from radiation.

In the absence of contraindications treatment is with LMWH16:


  • Heparin does not cross the placenta and therefore does not affect the fetus
  • LMWH is given subcutaneously and can be self-administered, allowing outpatient management
  • LMWH has a more predictable dose response allowing the doses to be based upon patient weight
  • For treatment of DVT, LMWH should be given 12 hourly to minimise peaks and troughs
  • Aim for antiXa levels of 0.4–1.0 U/ml; may be variable between laboratories and depends on the type of LMWH used
  • It may be possible to reduce the dose of LMWH to a high prophylactic dose once there has been complete resolution of symptoms.
  • Heparin-induced thrombocytopenia (HIT) is rare in pregnancy but the platelet count should be checked 5–7 days after starting therapy17
  • A small proportion of patients develop cutaneous allergy and may require changing to a different LMWH
  • A degree of cross-reactivity exists18 and alternative anticoagulants such as fondaparinux (Arixtra ) may be required
  • Anticoagulation should be continued for at least 6 months after the thrombotic event and should not be stopped before 6 weeks postpartum

Midwifery Management and Care


  • The mother should be taught correct self-injection technique
  • Ensure that she is given a sharps bin and knows how to dispose of sharps safely
  • The side effects of heparin should be discussed:

    • osteoporosis
    • HIT
    • cutaneous allergy

  • Reinforce general antithrombotic advice regarding hydration, mobility, leg care and avoidance of unnecessary long journeys
  • Ensure that compression stockings have been prescribed, are a good fit and encourage compliance
  • Graduated elastic compression stockings should be worn on the affected leg following proximal DVT for at least 2 years, to reduce the incidence of severe post-thrombotic syndrome7,6,19
  • Ensure that the woman is seen by an anaesthetist prior to delivery
  • Be aware of, and report any signs and symptoms of complications of this condition
  • In particular be aware of the risk of a DVT causing pulmonary embolism








Labour Issues

The intrapartum period is associated with an increase in both thrombotic and bleeding risks, and a careful assessment of these risks needs to be undertaken when planning safe management for the patient.

Ideally women should be allowed to labour spontaneously, as this reduces the need for obstetric intervention. However, depending on staffing levels, some centres may prefer a planned delivery.

Regional anaesthesia carries a possible risk of significant spinal bleeding and should be avoided within 12 hours of a prophylactic dose of LMWH and within 24 hours of a treatment dose.

General anaesthesia is associated with a higher thrombotic risk due to immobility, but may have to be considered for a caesarean section if temporary interruption of heparin is not thought suitable.

Prolonged labour and dehydration increase thrombotic risk.








Medical Management and Care

An intrapartum care plan must be worked out on an individual basis with each patient, involving the consultant obstetrician, consultant haematologist and consultant anaesthetist.

Women who are admitted in spontaneous labour or for a planned delivery will have been advised to omit their LMWH injection at the onset of contractions. This should avoid the problem of having an anticoagulant effect at the time of delivery and facilitate the use of epidural anaesthesia.

Women who are considered to be at high risk of further veno-thrombotic events may need to be converted to intravenous unfractionated heparin. This allows more flexibility in controlling anticoagulation and minimises time with trough levels. The heparin would need to be interrupted temporarily for the second and third stages of labour. These women should not be given intramuscular injections or NSAIDs.

Midwifery Management and Care


  • TED stockings
  • Encourage mobility by changes of position in labour
  • Passive leg exercises if mother has an epidural
  • Ensure that the woman remains hydrated, and consider iv fluids if necessary
  • Avoid prolonged use of lithotomy position
  • Active management of third stage after vaginal delivery, including the use of intravenous oxytocin
  • Early suturing of perineal tears/episiotomy



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Related posts:

  1. ENDOCRINE DISORDERS
  2. MUSCULOSKELETAL DISORDERS
  3. NEOPLASIA
  4. HAEMATOLOGICAL DISORDERS

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Aug 8, 2016 | Posted by in GYNECOLOGY | Comments Off on THROMBO-EMBOLIC DISORDERS

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