DVT & PE

1. DVT & PE By Dr. Khattab KAEO Prof. of Obstetrics and Gynaecology Faculty of Medicine, Al-Azhar University, Damietta

2. Incidence = 0.6 in 1000 pregnancy. Pregnan increases the risk by 6-10-x The risk is 3.5-x greater after delivery than during pregnancy. The risk is 2-4-x the risk with COC pills; & = 6-x the risk in general popul. females

3. Risk factors in pregnancy: -Alteration in thromb & clot lysis systems. This plays a minor role in VTE in pregn. except in cases of dehydration as in hyperemesis gravidarum, and if the intravascular fluid vol. is reduced as in preeclampsia. Thrombophilias play an increasing role. - Venous stasis caused by the uterus, decreased venous tone and decreased circulation time (partly due to reduced activity) Other factors not specific to pregnancy that cause venous stasis include plane journey of >3 h and bed rest. -Vascular damage canbe caused by hypert surgery & infection. The risk after CS is 5-x > after vaginal delivery.

4. - Other factors include:*Age, ≥3 parity, use of estrogen to suppress lactation, sickle cell anemia, smoking & paraplegia. Anemia, dehydration, congestive cardiac failure, thrombophilias and cancer. *Recurrence rate of thromboembolism is 11%. The previous VTE could be: ● Unprovoked VTE: This is associated with increased risk of recurrence compared with those provoked by a temporary risk factor. ● estrogen-provoked (estrogen-containing contra cep. or preg) VTE: Risk of recurrence = 10%. ●Thrombophilia or family history-associated VTE: Heritable thrombophilia is a weak risk factor. ●Temporary risk factor (eg major trauma or surgery): The risk of antenatal recurrence is very low.

5. Stratify women with previous VTE into: 1-Very high risk: Women with recurrent TE associated with either antithrombin deficiency or the PAPS. These women require LMWH either high prophylactic (/12h) or weight-adjusted (75% of treatment dose) antenatally & for 6 w postpartum or until converted back to warfarin. 2- High risk: Women in whom VTE was unprovoked or related to estrogen or who have other risk factors, a family history of VTE in a 1st-degree relative (sugges of thrombophilia) or a documented thrombophilia. These women require thromboprophylaxis with LMWH antenatally & for 6 w postpartum. 3- Intermediate risk: Women in whom VTE was pro-voked by a transient major risk factor and who have no other risk factors. In these women, prophylaxis with LMWH can be withheld antenatally, provided that no additional risk factors are present (in which case they should be offered LMWH). They require close surveillance for the development of other risk factors. They should be offered thromboprophylaxis with LMWH for 6 w postpartum.

6. *Gross varicose veins: symptomatic, above knee or with associated phlebitis/ edema/skin changes. *Obesity: >80 kg or BMI >30 kg/m2 pre-pregnancy or in early pregnan. Obesity is a moderate risk factor for TE. Over-Wt (BMI 25–30) is a weak risk factor.

7. Screening is indicated only in recurrent cases particularly if thrombosis is arterial, in atypical sites or associated with bad obstetric history. Screen for LA and aCL antibodies. If there is a family history, screen for inherited thrombophilias, homocystinuria & abnormal forms of fibrinogen. Risks: TE is now the leading cause of maternal mortality (11%in the UK). Deaths are evenly distributed between the antepartum & post-partum periods. The antepartum cases are evenly distributed between the 3 trimesters. The 1st w after delivery is the most dangerous period with the 1st 24h constitutes a partic. critical period.

8. Treatment:First ensure objective diagnosis because of the problems of treatment in the index pregn. & prophylaxis in the future pregnancies. Recognize predisposing factors & use prophylaxis in high-risk people Prophylaxis: All women should undergo a documented assessment of risk factors for VTE. It should constitute a principal part of routine history taking. 70% of fatal & non-fatal antenatal PE have identif. risk factors. LMWH reduces VTE risk in medical and surgical patients by 60% and 70%, respectively. Women with asymptomatic inherited or acqu. thromboph may be managed with close surveillance. However, in women with antithrombin deficiency, those with >1 thrombophilic defect or those with additional risk factors prophylaxis with LMWH is consid. Women with antithrombin deficiency (particularly type-1) have a very high risk of recurrence and may require intermediate or ttt doses of LMWH in pregnancy. Women with previous TE. The risk of recurrence appears to be constant over the whole period of pregnancy. All women with prior VTE should receive postpartum prophylaxis. For the purposes of antenatal risk assessment, women with previous VTE can be stratified into those with recurrent or single previous VTE.

9. Single previous VTE patients may be divided into those with ● unprovoked VTE. ● estrogen-provoked (E-containing contraception or pregnancy) VTE ● thrombophilia or family history-associated VTE. ● temporary risk factor (e.g. major trauma or surgery) associated VTE.

10. Many individuals with recurrent VTE will be on warfarin Women should be counselled about the risks of warfarin to the fetus and advised to change to LMWH as soon as pregnancy is confirmed, ideally within 2 w of the missed period and before the 6th w Women not on warfarin should be advised to start LMWH as soon as they have a +ve pregnancy test. Unprovoked VTE is associated with an increased risk of recurrence (6%) compared with those provoked by a temporary risk factor that is no longer present. When the previous VTE was associated with E-contain. contraception or during previous pregnancy, the recurrence rate is approximately 10%. Most of the recurrences (71%) are antenatal compared with 54% in the unprovoked group.

11. Heritable thrombophilia is at most a weak risk factor for recurrent VTE during pregnancy (RR 1.9). Testing for thrombophilia will therefore not usually influence thromboprophylaxis in the current pregnancy unless detected in a woman with a prior VTE related to a temporary risk factor. Investigate for thrombophilia in the latter group when the provoking stimulus was minor (such as long-distance travel) but not where it was major (such as surgery or major trauma with prolonged immobility or cancer). VTE resulting from a transient major risk factor carries very low risk of antenatal recurrence.

12. Patients with a single attack of TE outside pregnancy are considered “low-risk” patients if there is no family history of TE & no thrombophilia. They are treated with aspirin 75 mg bd throughout pregnancy switching to heparin at delivery.

13. Women with previous TE are to be stratified into: ● Very high risk: Women with recurrent TE associated with either antithrombin deficiency or the APS (who will often be on long-term oral anticoagulation).These women require high prophylactic (12-hourly) or Wt-adjusted (75% of ttt dose) antenatally & for 6w PP or until converted back to warfarin. ● High risk: Women in whom TE was unprovoked, idiopathic or related to E or who have other risk factors a family history of TE in a 1st-degree relative or a documented thrombophilia. These women require prophylaxis with LMWH antenat & for 6 weeks PP. ● Intermediate risk: Women in whom TE was provoked by a transient Mj risk factor that is no longer present & who have no other risk factors They require close surveillance for the develop-ment of other risk factors. They should be offered prophylaxis with LMWH for 6 w PP.

14. ≥3 risk factors (other than previous TE or thrombophilia) and “high-risk” patients with multiple episodes of TE &/or a family history of TE or thrombophilia of course warrant heparin prophylaxis starting in the 2nd ½ of pregnancy to balance the risks Vs benefits of heparin exposure. LMWH at the lowest doses when given for >8 w. When to start heparin prophylaxis? At least 4-6 w in advance of the gestation at which the previous event(s) occurred. If previous thrombosis was not in pregn., start after the 20th w. Women receiving LMWH should be advised that, if they have any vaginal bleeding or once labour begins, they should not inject any further LMWH. They should be admitted.

15. Recommendations for thromboprophylaxis after delivery:≥2 persisting risk factors (other than previous TE or thrombophilia) LMWH should be given for 7 days. The same is recommended for women with BMI >40kg/m2 & for women who have had emergency CS oran elective CS + ≥1 additional risk factors. Graduated compression stockings in addition to LMWH are given to women with ≥3 persisting risk factors.All women with asymptomatic thrombophilia should be given LMWH for ≥7 days following delivery, even if they were not receiving antenatal prophylaxis. This could be extended to 6w if there is family history or other risk factors present. Women with VTE before the current pregnancy should be offered LMWH for 6w following delivery. In women who have additional persistent (lasting >7 days PP) risk factors, such as wound infec., prophylaxis should be extended for up to 6w or until the additional risk factors are no longer present.

16. Active treatment:Acute phaseHospitalisation Heparin: Therapy should be commenced in suspected cases until the diagnosis is refuted 5000 U iv. then 1600 U/h by infusion (40000 U/day) for 7-10 days, until reaching a bl level of 0.6U/ml or APTT 1.5-2-x the control; given in 10-20 ml saline. Antidote is protamine SO4 Thrombolytic therapy: normal pulmonary capillary bl vol & pulmonary diffusing capacity in addition to earlier resolution & less post-phlebitic leg symptoms. It may cause relative uterine atony due to the interference of FDPs with uterine contraction. Surgery: Venous plication or insertion of vena caval umbrella prevents PE in case of ilio-femoral DVT. It is indicated where anti-coagulant therapy is strictly contraindicated as in intracranial hage. Pulmonary embolectomy is considered in the following cases: 1-shocked cases of PE 2- any of the following features 1-h later: a- S Bl P <90mm Hg; b- PaO2 <60mmHg; c- Urine output <20 ml/h.

17. Chronic phase for up to several months Heparin is assayed by anti-Xa as frequent as ANC visits. This is difficult; TT is a sensitive alternative. If the level >0.2U/ml, the dose should be reduced. Heparin is continued for the remainder of pregnancy & until 6 w PP or for 3 months which is longer (SQ) discontinued 24h before induction of labour & resumed immediately PP. Providing APTT, TT & platelet count are normal there is no bleeding risk at delivery, and epidural block & CS are quite safe. After delivery reduce the dose to 7500Ux2 daily -due to decrease in bl vol- for 6w, or only for 1 w then replaced by warfarin for 5w. Warfarin should be initiated within 24h of delivery & once a therapeutic INR of 2-3 is achieved, heparin is discontinued, & warfarin is maintained for ≥6 w. While warfarin requires Rpt monitoring by PT, heparin does not require monitoring after the 1st w. Warfarin is given daily, the first 2 doses are 10 mg each then the INR is checked before giving the 3rd dose (for the ttt of DVT INR should be 2-3; for pro-phylactic therapy a value of 2-2.5 is sufficient; with prosthetic valves INR should be 3-4.5).

18. DVT - DVT often develops without symptoms or signs. - There may be mild pyrexia. - Tender oedematous calf. However, 50% of patients with tender swollen calf do not have DVT. Persistent leg swelling and/or pain with tenderness rises suspicion. The affected leg may feel warmer. Careful tape measurement may reveal some swelling compared with the other leg. Although deep in the groin the femoral vein may be palpable in the condition of Phlegmasia Albna Dolens (extreme thrombosis with complete block of the femoral vein causing solid oedema & marbled appearance of the superficial veins). The condition is very painful.

19. - 40% of PP DVT occurs after discharge. - It is 8-x more common in the left leg (90% of cases); signs and symptoms isolated to the right leg reduce the probability of DVT. • Most cases (72%) are iliofemoral. C/o lower abdominal pain, O/E pyrexia, in addition to leucocytosis. Differential diagnosis is UTI and appendicitis. - Clinically DVT should be differentiated from Baker’s cyst, muscle strain or haematoma, myositis, neurogenic pain and arthritis.

20. - C reactive ptn: Normal values R/O DVT -Impending plethysmography is inexpens bedside non-invasive & sensitive (to obstruc. in venous outflow). It is effective at testing for the presence or development (impending)of thrombosis particularly proximal DVT. It is per-formed in the Lt lateral position; the position should also be adopted for 20 min before testing. +ve tests (particularly in the 3rd trimester) should be confirmed by venography or US because what constitutes +ve tests in pregnancy is not yet known. Serially -ve tests rule out clinically significant DVT (anticoagulant ttt can be withheld safely).

21. - Ultrasound is highly effective (sensitivity & specificity = 97% for proximal vein thrombosis). The clot may be seen & the vein is incompressible and does not dilate during a Valsalva manoevure. US is helpful at identifying other causes of leg swelling such as haematoma or Baker’s cyst. - Venography: In spite of being ‘the gold standard’ for the diagnosis of DVT, is reserved for centers where plethysmography or ultrasound are not available, and to confirm a +ve plethysmography test. It is painful; costly; contrast  nephrotoxicity & allergy; and shielding reduces visualization of the iliac veins & isolated thrombosis in them will not be detected. - Specificity and sensitivity of Doppler ultrasound to diagnose DVT in proximal veins are higher than in distal veins. - Isotop localisation: Radioactive iodine-labelled fibrinogen is injected. It will be deposited at the site of the thrombus, and this can be detected using a scintillation counter over the suspected vein. The thyroid must be protected by earlier injection of sodium iodide. The technique is only applicable postnatally to non-lactating women.

22. Risks 1- Proximal DVT has a high probability of major embolization to the lungs and should be treated. Calf vein thrombosis  negligible risk of embolization provided it remains confined to the calf. 2- Postphlebitic syndrome (chronic venous insufficiency): Swelling, varicose veins, pain, eczema, skin changes and ulceration.

23. Pulmonary embolism The risk of pulmonary embolism with thrombosis limited to calf muscles = 1%, but rises to 50% if the ilio-femoral vessels are involved. However, in up to 70% of cases there are no signs of DVT. Risk of pulmonary embolism in treated cases of DVT is still high although much less than in untreated cases (4.5:20%). Other risk factors include excessive blood loss and blood group other than O.

24. Diagnosis Massive PE = 60% of pulmonary circulation is involved. It presents with collapse, chest pain (occasionally abdominal pain probably due to irritation of the diaph) breathlessness & cyanosis. O/E: There is hypo-tension, may be a 3rd heart sound, parasternal heave & elevated jugular venous pressure. Major embolism is often preceded by small emboli with syncope, pleuretic chest pain, tachypne breathlessness cough & unexplained pyrexia. Bronchospasm may be a feature. Chest X-ray is useful in excluding other diseases&interpreting the ventilation /perfusion lung scan. lLvel of OH-butarate dehydrogenase is high. ECG: There is right heart strain. S1 Qiii Tiii are diagnostic of major PE. ECG & CXR may be normal. ABG has false +ve & false -ve results although with PaO2 <70mmHg & normal or low PaCO2 the chest symptoms are likely to be due to PE. Pulmonary angiography: In spite of being ‘the gold standard’ for the diagnosis of PE, it is invasive; costly; contrast  allergy; in addition to exposing the patient to high levels of radiation. It is indicated in severe cases in which surgery may be required. In the non-acute situation V/Q lung scan is the pivotal test having a very high -ve predictive value (ttt can be withhold safely) “High-probability” lung scan = segmental or large subsegmental perfusion defect with normal ventilation “Non-high-probability” lung scan should be followed by U.S. or IPG. If -ve, pulmonary angiography is performed. If the patient does not die, she will recover completely with few patients have symptomatic pulmonary hypertension & abnormal lung function tests. Lung scan if normal excludes PE. A large perfusion defect with normal CXR is likely to be due to PE. A reduction in perfusion with maintenance of ventilation indicates PE. In the future low D-dimer FDP will be used to exclude PE.

25. Treatment Massive pulmonary embolus: Cardiac arrest procedure (prolonged cardiac massage may break up the original clot) + heparin 20 000U i.v. to reverse the broncho- and vaso-constrictions caused by the release of serotonin from platelets. Acute and chronic phases.

26. Thank you