Venous thromboembolism (VTE)

in pregnancy – 7 years’ experience

관동의대 제일병원 내과

박 정 배

2009년 10월 8-10일추계심장학회 Hilton convention center 서울

Case 35세 여환

Chief complaintDyspnea, dizziness onset) POD#6

Present illness

Case

10일전 IUP 38+2 weeks 제왕절개 분만. 4일전 DOE (III) 증상 발생내원 20분 전 20초간의 syncope 로 ER

Vital sign ;115/88mmHg – 113회/min – 22회/min , 37.2°C

� Lab

aPTT (25~40seconds) 39.4

PT (INR) (0.84~1.16) 1.39

D-dimer (0~0.5 ug/mL) >20

Troponin-I rapid assay Negative

CPK (24~170 U/L) 90

�� EF ; 52%EF ; 52%

�� RV volume overloadingRV volume overloading

�� D shaped of LVD shaped of LV

� Echocardiogram

CPK (24~170 U/L) 90

CK-MB (0~4.94 ng/ml) 2.40

BNP (0~100 pg/mL) 807

�� RVERVE

�� Dilated IVCDilated IVC

�� TR severe with pulmonary HTNTR severe with pulmonary HTN

� Nonspecific ECG

Massive pulmonary embolism

Right side heart failure

Chest CT

� Incidence and Risk

� 1 in 500 ~ 2000 pregnancies (0.025 ~ 0.10 %)

� 4 ~ 50 x ↑ in pregnant vs non-pregnant women

� risk factor : Pregnancy & puerperium itself

� postpartum > antepartum

Incidence and risk of VTE

Epidemiology

� postpartum > antepartum

� 20 % of the maternal mortality

� Risk of deep vein thrombosis (DVT)

� C-sec delivery (x2) > vaginal birth

� left leg > right leg

� compression of left iliac vein by right iliac artery

� compression of IVC by gravid uterus

Incidence of venous thromboembolism

in pregnancy and puerperium

0.028747

%

Norwegian, n=613 Cheil General Hospital, n=17

0.028747

0.036521

0.062254

0.041475

<

<

<≅

≅

<

>

Korean J Med 75:658-664, 2008Am J Obstet Gynecol 2008;198:233.e1-233.e7.

Virchow’s classic triadof risk for VTE

Pathogenesis

� Pulmonary embolism

� Deep-vein thrombosis

VTE

: Venous

Thrombo-

Embolism

Hyper-

coagulability

Vascular

Injury

Venous

stasis

� Deep-vein thrombosis

Risk of VTE by Type of Thrombophilia*

Thrombophilia Odds Ratios

Factor V Leiden– homozygosity 34.40 (9.86, 120.05)

Factor V Leiden– heterozygosity 8.32 (5.44, 12.70)

Prothrombin gene mutation–homozygosity 26.36 (1.24, 559.29)

Prothrombin gene mutation–heterozygosity 6.80 (2.46, 18.77)

Protein C deficiency 4.76 (2.15, 10.57)

Protein S deficiency 2.19 (1.48, 6.00)

Antithrombin deficiency 4.76 (2.15, 10.57)

James AH.2009 ATVB* 20% to 50% of VTE in pregnancy

Prevalence of congenital thrombophilia and the

associated risk of thromboembolism during

pregnancy in a European population

Jacobsen AF et al. 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

Risk patterns of VTE

• assisted • preeclampsia

Antenatal PostnatalOurs

Postnatal, n=15/17)

• assisted

reproduction

• gestational

diabetes

• C- section

• placenta previa

• assisted

reproduction

Am J Obstet Gynecol 2008;198:233.e1-233.e7

• preeclampsia

• C- section

• multiple preg.

Korean J Med 75:658-664, 2008

Risk Factor Odds Ratio Confidence Interval

Medical conditionsHeart disease 7.1 6.2 ~ 8.3

Sickle cell disease 6.7 4.4 ~ 10.1

Lupus 8.7 5.8 ~ 13.0

Obesity 4.4 3.4 ~ 5.7

Anemia 2.6 2.2 ~ 2.9

Diabetes 2.0 1.4 ~ 2.7

Medical Conditions and Complications of Pregnancy and

Delivery Associated With an Increased Risk of VTE in Pregnancy

Diabetes 2.0 1.4 ~ 2.7

Hypertension 1.8 1.4 ~ 2.3

Smoking 1.7 1.4 ~ 2.1

Complications of pregnancy and deliveryMultiple gestation 1.6 1.2 ~ 2.1

Hyperemesis 2.5 2.0 ~ 3.2

Fluid & electrolyte imbalance 4.9 4.1 ~ 5.9

Antepartum hemorrhage 2.3 1.8 ~ 2.8

Cesarean delivery 2.1 1.8 ~ 2.4

Postpartum infection 4.1 2.9 ~ 5.7

Postpartum hemorrhage 1.3 1.1 ~ 1.6

Transfusion 7.6 6.2 ~ 9.4

James AH.

2009 ATVB

Symptoms No. % Signs No. %

Dyspnea 8 62% Tachcardia (PR>100/min) 11 85%

Chest pain 4 31% Tachypnea (RR>20/min) 8 62%

Symptoms and signs of Pulmonary embolism

Diagnosis

Chest pain 4 31% Tachypnea (RR>20/min) 8 62%

Cough 2 15% ↓ breathing sound 6 46%

Sweating 2 15% ↓ BP 4 31%

Syncope 1 8% Cyanosis 4 31%

Hemoptysis 1 8% Convulsion 2 15%

No symptom 0 0 Shock 2 15%

Pitfall of clinical examination of VTE

� Clinical Dx of DVT & PE : insensitive, nonspecific

� Pregnant women, Lower Ext. swelling & discomfort

common in advanced pregnancy� common in advanced pregnancy

� Dyspnea, the most frequent symptom of PE

� occurs in up to 70 % of normal pregnancies

� often stabilizing near term

Diagnostic

algorithm1

2

3

(Magnetic resonance direct thrombus imaging)

Marik PE_VTE and Preg_2008 NEJM

4

Characteristics of P.Emb : Cheil Gen. Hosp

Case Age Delivery Symptoms Onset

(days)

Pulse

(/min)

D-dimer

(µg/mL)

Chest CT Pul pre

mmHg)

Tx

1 32 C/S* Dyspnea 5 105 >20 Rt. 29.3 -

2 32 C/S Chest pain 3 95 >20 Lt. 39.2 -

3 32 eC/S Dyspnea 2 110 7.8 Lt. - -

4 31 eC/S Dyspnea 3 95 18.8 Rt. - -

5 28 NSVD Convulsion 1 100 19.9 Lt. 30.3 -

6 35 C/S Dyspnea, Chest pain 2 105 13.0 Lt. main 40.8 +

7 36 C/S Chest pain 6 110 17.5 Lt. main 41.9 +

8 35 eC/S Convulsion 1 105 16.3 Rt. main - +

9 33 eC/S Dyspnea 2 110 7.8 Both 35.5 +

10 29 eC/S Dyspnea 2 105 11.2 Rt. 38.0 +

11 35 eC/S Chest pain 2 105 8.9 Both - +

12 31 eC/S Dyspnea 3 120 16.4 Both 37.6 +

13 35 C/S Dyspnea 10 130 >20 Both main 47.8 Embolectomy

C/S*: Cesarean section, eC/S: Emergency Cesarean section, NSVD: Normal spontaneous vaginal delivery +, anticoagulant

제일병원에서는 II : after C-section

C-Sec 분만후

tachycardia,

tachypnea,

chest pain

D-dimer>5

*

P.Emb CT Protocol ?

?

� Unfractionated heparin� heparin level : 0.2 ~ 0.4 U/mL (protamine titration assay)

� PTT : 1.5 ~ 2.3 times the control value

� LMW heparin, but preferable� little information on appropriate dosing in pregnancy

Anticoagulation

Treatment

� little information on appropriate dosing in pregnancy

� anti-Factor Xa level : 0.5 ~ 1.2 U/mL, 4 hours after inj.

� Enoxaparin : 1mg/kg twice a day

� Total duration of anticoagulation : 3 ~ 6 months

� After delivery : 4 ~ 6 week course of warfarin� INR 2.0 ~ 3.0

� safe during lactation

Inferior vena cava filter

� anticoagulation contraindicated

(recent surgery, hemorrhagic

stroke, active bleeding)

� anticoagulation : ineffective

� pulmonary vascular bed :

significantly compromised

(massive PE, chronic

thromboembolic pulmonary HTN)

Thrombolytic therapy

• maternal hemorrhage

• massive pulmonary embolism with hemodynamic instability

Operation: Embolectomy

Heparin

DVT, n=7 Delivery

warfarin4 3

DVT and PE, antenatal and postnatalCheil Gen. Hosp.

Heparin

PE, n=20

Heparin

warfarin1 19*

1 with heparin use

2, simultaneously with DVT*

PTE and DVT

79%~90%50%

Results on 3 or 6- month recovery

Heparin (+) 17 (65%) 14 (82%)* 3 (18%) 0.53

VTEVTE RecoveryRecovery

++

RecoveryRecovery

--

PP--valuevalue

Cheil Gen. Hosp.

No different effect of anticoagulant treatment on recovery of VTE

Heparin (-) 9 (35%) 8 (100%) 0

Warfarin (+) 11 (42%) 8 (72%) 3 (28%) 0.06

Warfarin (-) 15 (58%) 15 (100%) 0

*, one patient received embolectomy

Prophylaxis of VTE according to risk stratification

� Low risk : early ambulationcesarean delivery for uncomplicated preg, without risk factors

� Moderate risk: LMWH or compression stockings• age > 35 yr

• obesity, BMI >30

• parity >3

• gross varicose veins

C-sec 후 12시간

• gross varicose veins

• current infection

• preeclampsia

• immobility for >4 days before operation

• major current illness

• emergency cesarean section during labor

� High risk: LMWH & compression stockings(+) ≥ 2 risk factors

cesarean hysterectomy

previous DVT or known thrombophilia

Strategy for VTE during pregnancy and puerperium

Suspicion

D-dimer & CT

D-dimer & US

(-)ambulation

Anticoagulation, or

thrombolytic, or

embolectomy

Or ambulation?

Thrombophilia test If preg. planned.Park JB 2009

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