6º Curso Nacional de Atualização em Obstetrícia e

Ginecologia

Aula 5: Trombofilias na gestação

Módulo 2: Intercorrências clínicas e

obstétricas 1

Dr. André Luiz Malavasi

Tromboembolismo venoso no ciclo
gravídico-puerperal
TEV
20

primeiro segundo terceiro puerpério

não grávida
trimestre trimestre trimestre
 Cascata da coagulação
via intrínsica via extrínsica

superfície lesão tecidual

Calicreína

XII XIIa fator tecidual

XIa
XI Ca
XI IXa
fosfolípide +
Ca
↑↑↑ VIIIa
VIIa ↑↑↑ VII
↓↓PS / PC

antitrombina
X Xa

V XIII
Va

Protrombina
ç Trombina ç

IXa

Fibrinogênio ↑ 20 a Fibrina ç ç fibrina

Malha de
200%
 Risco de TEV na gestação aumenta 4 a 5 vezes

Risco de TEV no puerpério aumenta 20 vezes

James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the
postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194:1311–1315.
 Incidência de fenômenos tromboembólicos na gestação:
2:1000 partos

Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ, III. Trends in the incidence of
venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann
Intern Med. 2005;143:697–706
1- Cockett FB, Thomas ML. The iliac compression syndrome. Br J Surg.1965;52:816 – 821.
2- James AH, Tapson VF, Goldhaber SZ. Thrombosis during pregnancy and the postpartum
period. Am J Obstet Gynecol. 2005;193:216–219.
 Fatores de Risco

RR = 1,6

RR = 2,5

RR = 2,3

RR = 2,1

RR = 4,1

RR = 7,6

Nationwide Inpatient Sample - 14.335 pacientes

Venous Thromboembolism in Pregnancy, Andra H. James Arterioscler Thromb Vasc Biol 2009;29;326-
331, DOI: 10.1161/ATVBAHA.109.184127
 Fatores de Risco

RR = 7,1

RR = 6,7

RR = 8,7

RR = 4,4

RR = 2,0

RR = 1,8

RR = 1,7

Nationwide Inpatient Sample - 14.335 pacientes

Venous Thromboembolism in Pregnancy, Andra H. James Arterioscler Thromb Vasc Biol 2009;29;326-
331, DOI: 10.1161/ATVBAHA.109.184127
 Fatores de Risco

1-Macklon NS, Greer IA. Venous thromboembolic disease in obstetrics and gynaecology: the Scottish experience. Scott Med J.
1996;41:83–86. 85.

2-Jacobsen AF, Drolsum A, Klow NE, Dahl GF, Qvigstad E, Sandset PM. Deep vein thrombosis after elective cesarean section.
Thromb Res. 2004;113:283–288.
 Fatores de Risco

1-Sanson BJ, Lensing AW, Prins MH, Ginsberg JS, Barkagan ZS, Lavenne- Pardonge E, Brenner B, Dulitzky M, Nielsen JD, Boda Z, Turi S, Mac Gillavry
MR, Hamulyak K, Theunissen IM, Hunt BJ, Buller HR. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost.
1999;81:668–672.

2-Lepercq J, Conard J, Borel-Derlon A, Darmon JY, Boudignat O, Francoual C, Priollet P, Cohen C, Yvelin N, Schved JF, Tournaire M, Borg JY. Venous
thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. Bjog. 2001;108: 1134 –1140.
Trombofilia e risco de TEV

Trombofilia RR

Fator V (heterozigose) 9,3

Fator V (homozigose) 34,4

Protrombina mutante (heterozigose) 6,8

Protrombina mutante (homozigose) 26,4

Deficiência de proteína C 4,8

Deficiência de proteína S 3,2

Deficiência de antitrombina 4,7

Robertson et al, 2006

Efeitos colaterais ao uso de heparinas

Sangramento em 1,98%
Efeitos colaterais ao uso de heparinas

Osteopenia em 30% das gestantes

Efeitos colaterais ao uso de heparinas

HIT em 3% das gestantes

 prevalência na população risco de TEV na gestação risco de TEV na gestação
geral [ sem história] [ com história]

FVL heterozigoto 15% < 0,3% 10%

FVL homozigoto < 1% 1,5% 17%

Def. proteína S 0,15% 0,1% 22%

Def. proteína C 0,4% 0,8% 17%

MP homozigoto 5% < 0,5% > 10%

MP heterozigoto < 1% 2,8% > 17%

Riscos relativos relacionados à trombofilias
Tipo de trombofilia AB 1o tri Ab repetição Perda de Perda de Pré DPP RCF

Segundo terceiro eclampsia

trimestre trimestre

Fator V de Leiden
2.71 NA NA 1.98 1.87 8.43 4.64
homozigoto

Fator V de Leiden
1.68 1.91 4.12 2.06 2.19 4.70 2.68
heterozigoto

Mutação G202201A da
2.49 2.70 8.60 2.66 2.54 7.71 2.92
protrombina heterozigoto

MTHFR C677T homozigoto 1.40 0.86 NA 1.31 1.37 1.47 1.24

Deficiência de antitrombina 0.88 NA NA 7.63 3.89 1.08 NA

Deficiência de proteína C 2.29 NA NA 3.05 5.15 5.93 NA

Deficiência de proteína S 3.55 NA NA 20.09 2.83 2.11 NA

SAF 3.40 5.05 NA 3.30 2.73 1.42 6.91

Hiperhomocisteinemia 6.25 4.21 NA 0.98 3.49 2.40 NA

Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Shannon M. Bates, MDCM Ian A. Greer, MD, FCCP; Saskia Middeldorp, MD, PhD; David L. Veenstra, PharmD, PhD; Anne-Marie Prabulos, MD; and Per Olav Vandvik , MD ,
PhD
Fatores de risco MAIORES (Risco > 6 vezes):
presença de pelo menos UM destes fatores traz risco > 3% de TVP/TEP no pós-parto
Imobilização (restrição ao leito > 1 semana no período ante parto)

Hemorragia puerperal ≥ 1.000 ml com cesárea

TVP/TEP prévios

Pré eclâmpsia com RCF

Deficiência de antitrombina

Fator V de Leiden homozigoto ou heterozigoto

Mutação G202201A da protrombina homozigoto ou heterozigoto

Lupus

Cardiopatias

Anemia falciforme

Hemotransfusão

Infecção puerperal

Fatores de risco MENORES (Risco > 6 vezes QUANDO COMBINADOS):

presença de pelo menos DOIS destes fatores isolados ou UM associado à cesárea de
emergência traz risco > 3% de TVP/TEP no pós-parto
IMC > 30 kg/m2

Gemelidade

Hemorragia pós parto >1 L

Tabagismo >10 cigarros /d

RCF

Deficiência de protein C

Deficiência de protein S

Pré-eclâmpsia

Chest February 2012 141:2 suppl e691S-e736S; doi:10.1378/chest.11-2300

 a
HZ FVL / PM outras trombofilias AP AF G P Referência 9 ACCP

8.2.3
  ✓ ✓ 8.2.1

  ✓ ✓ 9.2.1

 ✗ ✓ 9.2.3

8.2.3
  ✓ ✓ 8.2.1

  ✗ ✓ 9.2.2

 ✗ ✗ 9.2.4
 Anticoagulação na Gestação

Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins-Obstetrics (2012) Practice Bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 120(6):1514–1521

Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David
M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE (2014) Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 36(6):527–53

Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.

Mclintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, Muller P, Tran H, Walters BNJ, Young L (2012) Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the
postpartum period. ANZJOG 52:14–22

Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians (2012) 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 141(2 Suppl):e691S–e736S
 Anticoagulação na Amamentação

Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins-Obstetrics (2012) Practice Bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 120(6):1514–1521

Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David
M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE (2014) Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 36(6):527–53

Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.

Mclintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, Muller P, Tran H, Walters BNJ, Young L (2012) Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism i
n pregnancy and the postpartum period. ANZJOG 52:14–22

Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians (2012) 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 141(2 Suppl):e691S–e736S
 Hospitalização

Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins-Obstetrics (2012) Practice Bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 120(6):1514–1521

Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David
M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE (2014) Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 36(6):527–53

Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.

Mclintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, Muller P, Tran H, Walters BNJ, Young L (2012) Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism i
n pregnancy and the postpartum period. ANZJOG 52:14–22

Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians (2012) 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 141(2 Suppl):e691S–e736S
 Indicações de HNF

Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins-Obstetrics (2012) Practice Bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 120(6):1514–1521

Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David
M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE (2014) Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 36(6):527–53

Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.

Mclintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, Muller P, Tran H, Walters BNJ, Young L (2012) Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism i
n pregnancy and the postpartum period. ANZJOG 52:14–22

Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians (2012) 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 141(2 Suppl):e691S–e736S
 Meias de compressão graduada

Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins-Obstetrics (2012) Practice Bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 120(6):1514–1521

Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David
M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE (2014) Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 36(6):527–53

Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.

Mclintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, Muller P, Tran H, Walters BNJ, Young L (2012) Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism i
n pregnancy and the postpartum period. ANZJOG 52:14–22

Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians (2012) 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 141(2 Suppl):e691S–e736S
 Recomendações CHEST / IST

Para gestantes com risco adicional para TEV submetidas à

operação cesariana, recomenda-se o uso de meias elásticas ou
compressão pneumática intermitente

2C

The 9th ACCP Conference on Antithrombotic and Thrombolytic Therapy, Chest 2012
Chest February 2012 141:2 supple
691S-e736S; doi:10.1378/chest.11-2300
Chest February 2012 141:2 supple
691S-e736S; doi:10.1378/chest.11-2300
Cuidados no parto de gestantes com TVP/TEP
Cuidados no parto de gestantes com TVP/TEP

Parto programado a partir de 37 semanas

Quando utiliza AAS: suspender uma semana antes do parto

Suspender HBPM 12 / 24 h antes do parto (possibilita raquianestesia ou peridural)

Via de parto: indicação obstétrica

Re-introduzir HBPM 8 h pós-parto e mantê-los até o final da 6a semana

Na SAF com trombose vascular anticoagulação oral perene

Estimular a deambulação precoce e o uso de meias elásticas

drandreluiz@yahoo.com.br