venous thromboembolism (vte) in pregnancy –7 years’ experience · 2015-07-07 · anemia 2.6 2.2...
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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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