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Practice bulletins > #197 Inherited Thrombophilias in Pregnancy > Flashcards

#197 Inherited Thrombophilias in Pregnancy Flashcards

1
Q

What role does the decidual layer of the uterus play in hemostasis during pregnancy?

A

Plays a crucial role in prevention of hemorrhage during implantation, placentation and 3rd stage of labor

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2
Q

What obstetric conditions are seen with absent or impair decidua?

A

Ectopic pregnancy and placenta accreta

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3
Q

What role does the decidua play in development of DIC observed in decidual hemorrhage (ie, placental abruption)?

A

Decidual tissue factor can promote the intense hypofibrinogenemia and DIC

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4
Q

What factors in pregnancy contribute to the thrombotic potential of pregnancy?

A

Decreased anticoagulant activity, decreased fibrinolysis. Venous stasis in lower extrmities d/t compression of IVC and pelvic veins by enlarging uterus, a hormone-mediated increase in venous capacitance, insulin resistance, and hyperlipidemia.

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5
Q

Venous thromboembolism complicates x/1,000 pregnancies?

A

0.5-2 per 1,000 pregnancies

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6
Q

Venous thromboembolism accounts for what % of pregnancy-related deaths in the US?

A

9.2%

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7
Q

What is the risk of thromboembolism during pregnancy or postpartum compared to non pregnant patients (fold increase)?

A

4-5 fold increased risk

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8
Q

True or false, empiric treatment of identified thrombophilia carriers during pregnancy improve pregnancy outcomes?

A

False, has not been confirmed to confer any discrete benefit re: preg outcomes (eg fetal loss, PEC, FGR). Does help with thromboembolism prevention in at risk women though.

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9
Q

What is the prevalence (%) of Factor V Leiden heterozygotes in the population?

A

1-15%

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10
Q

What is the VTE risk (%) per pregnancy in someone heterozygous for Factor V Leiden (an no prior hx)?

A

0.5-3.1%

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11
Q

What is the VTE risk (%) per pregnancy in someone heterozygous for Factor V Leiden in patient with prior VTE?

A

10%

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12
Q

Of all cases of VTE during pregnancy, what % occur in women heterozygous for factor V Leiden?

A

40%

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13
Q

What is the prevalence (%) of homozygous factor V Leiden?

A

<1%

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14
Q

What is the VTE risk per pregnancy (%) in women homozygous for factor V Leiden w/ no prior VTE?

A

2.2-14%

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15
Q

What is the VTE risk per pregnancy (%) in women homozygous for factor V Leiden w/ prior VTE?

A

17%

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16
Q

Of all cases of VTE during pregnancy, what % occur in women homozygous for factor V Leiden?

A

2%

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17
Q

What is the prevalence (%) of prothrombin gene heterozygote?

A

2-5%

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18
Q

What is the VTE risk per pregnancy (%) for prothrombin gene heterozygote w/ no prior VTE?

A

0.4-2.6%

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19
Q

What is the VTE risk per pregnancy (%) for prothrombin gene heterozygoe w/ prior VTE?

A

> 10%

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20
Q

Of all VTE during pregnancy, what % occur in women heterozygous for prothrombin gene?

A

17%

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21
Q

What is the prevalence of prothrombin gene homozygote?

A

<1%

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22
Q

What is the VTE risk per pregnancy (%) with prothrombin gene homozygote w/ no prior VTE?

A

2-4%

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23
Q

What is the VTE risk per pregnancy (%) with prothrombin gene homozygote w/ prior VTE?

A

> 17%

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24
Q

Of all VTE during pregnancy, what % occur in women homozygous for prothrombin gene?

A

0.5%

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25
Q

What is the prevalence (%) of factor V Leiden/prothrombin gene double heterozygote?

A

0.01%

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26
Q

What is the VTE risk per pregnancy (%) for women with factor V Leiden/prothrombin gene double heterozygote w/ no prior VTE?

A

4-8.2%

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27
Q

What is the VTE risk per pregnancy (%) for women with factor V Leiden/prothrombin gene double heterozygote w/ prior VTE?

A

> 20%

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28
Q

Of all VTE during pregnancy, what % occur in double heterozygote for factor V Leiden/prothrombin?

A

1-3%

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29
Q

What is the prevalence (%) of Antithrombin deficiency?

A

0.02%

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30
Q

What is the VTE risk of antithrombin deficiency during pregnancy (%), with no prior VTE?

A

0.2-11.6%

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31
Q

What is the risk of VTE per pregnancy (%) with woman with antithrombin deficiency and prior VTE?

A

40%

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32
Q

Of all VTE during pregnancy, what % occur in women with antithrombin deficiency?

A

1%

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33
Q

What is the prevalence (%) of protein C deficiency?

A

0.2-0.4%

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34
Q

What is the VTE risk per pregnancy (%) in women with protein C deficiency w/ no prior VTE?

A

0.1-1.7%

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35
Q

What is the VTE risk per pregnancy (%) in women with protein C deficiency w/ prior VTE?

A

4-17%

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36
Q

Of all VTE during pregnancy, what % occur in women with protein C deficiency?

A

14%

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37
Q

What is the prevalence of protein S deficiency?

A

0.03-0.13%

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38
Q

What is the VTE risk per pregnancy (%) for women with protein S deficiency and no prior VTE?

A

0.3-6.6%

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39
Q

What is the VTE risk per pregnancy (%) for women with protein S deficiency and prior VTE?

A

0-22%

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40
Q

Of all VTE during pregnancy, what % occur in women with protein S deficiency?

A

3%

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41
Q

What is the prevalence (%) of the factor V Leiden mutation in caucasians, hispanic americans, african americans, asian americans, and native americans?

A 
Caucasian - 5.27%
Hispanic american - 2.21%
African american - 1.23%
Asian american - 0.45%
Native american 1.25%
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42
Q

By what mechanism of action does a mutation in factor V Leiden lead to a prothrombic state?

A

the mutation renders it refractory to proteoysis by activated protein C.

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43
Q

What prothrombin mutation leads commonly leads to a prothrombotic state, what kind of mutation?

A

Prothrombin G20210A mutation is a point mutation

44
Q

How does the prothrombin G20210A mutation lead to prothrombotic state?

A

Results in elevated circulating prothrombin levels

45
Q

What is a commonly used cutoff for protein C to be considered abnormal?

A

A protein C level less than 65% is typically considered abnormal

46
Q

Newborns who are homozygous for protein C can develop what rare condition, how does it present, what treatment is necessary?

A

Neonatal purpura fulminans, a rare life-threatening condition characterized by disseminated intravascular coagulation and hemorrhagic skin necrosis, and will require lifetime anticoagulation therapy

47
Q

Can you screen for protein S deficiency during pregnancy?

A

Not reliable, due to fluctuating levels of protein S binding protein during pregnancy

48
Q

Newborns who are homozygous for protein S can develop what rare condition, how does it present, what treatment is necessary?

A

Neonatal purpura fulminans, a rare life-threatening condition characterized by disseminated intravascular coagulation and hemorrhagic skin necrosis, and will require lifetime anticoagulation therapy

49
Q

Is it possible to have antithrombin deficiency with normal antigen levels?

A

Yes. Can have mutations that alter structure or function leading to decreased function

50
Q

What is the prevalence of heterozygous antithrombin deficiency in general population?

A

1 per 2,500

51
Q

In nonpregnant patients, how does the risk of VTE change (fold change) among antithrombin-deficient patients?

A

Risk increased more than 25-fold

52
Q

How does normal pregnancy affect the levels of antithrombin?

53
Q

What is the antithrombin activity level (%) in mild antithrombin deficiency?

A

Between 70 and 85%

54
Q

What is the risk of VTE in pregnant women with no prior VTE and a mild antithrombin deficiency?

55
Q

What is the risk of VTE in pregnant women with hx of thromboembolism, severe antithrombin deficiency (<60% activity)?

A

Risk as high as 40%

56
Q

What is the risk of VTE in women with antithrombin deficiency in the anepartum and postpartum period?

A

Antepartum - 7.3%

Postpartum 11.1%

57
Q

What is the most common cause of hyperhomocysteinemia?

A

Homozygosity for the MTHFR (methylenetetrahydrofolate reductase) gene mutation

58
Q

Does MTHFR (methylenetetrahydrofolate reductase) mutations increase risk of VTE?

A

Does not appear to, in pregnant and non pregnant women

59
Q

What associations are there between inherited thrombophilias and adverse pregnancy outcomes?

A

No or weak associations between inherited thrombophilias and adverse pregnancy outcomes

60
Q

Do inherited thrombophilias increase the risk of first trimester pregnancy loss?

61
Q

What is the recommendation for a women with prior pregnancy loss and inherited thrombophilia?

A

No anti coagulation. Consider ASA

62
Q

Should inherited thrombophilias be screened for in setting of stillbirth?

A

No. Only a weak association between Factor V Leiden mutation and stillbirth. No association with prothrombin or MTHFR mutations

63
Q

Is there an association between inherited thrombophilias and preeclampsia?

A

There is insufficient evidence to conclude that there is an association

64
Q

Is there an association between inherited thrombophilias and fetal growth restriction?

A

No significant associations

65
Q

Is there an association between inherited thrombophilias and placental abruption?

A

Insufficient evidence to establish a link between thrombophilias and placental abruption

66
Q

Is anticoagulation recommended to pregnant women with inherited thrombophilias as an intervention to prevent adverse pregnancy outcomes?

A

Insufficient evidence to recommend anticoagulation for this purpose

67
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: Personal hx of VTE, without recurrent risk factor, no prior thrombophilia testing

68
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: Personal hx of VTE, with recurrent risk factor, no prior thrombophilia testing

69
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: First-degree relative with a hx of high-risk inherited thrombophilia

70
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of fetal loss

71
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of placental abruption

72
Q

Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of fetal growth restriction

73
Q

What are the recommended inherited thrombophilia screening tests for women with personal hx of VTE?

A

Factor V Leiden mutation, prothrombin G20210A mutation, antithrombin, protein S, and protein C deficiencies

74
Q

How do you test for factor V Leiden mutation? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?

A

Activated protein C resistance assay; [reliable in pregnancy and acute thrombosis, not on anti-coagulation]

If screening abnormal send DNA analysis. [reliable in all settings]

75
Q

How do you test for prothrombin G20210A mutation? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?

A

DNA analysis. Reliable in all settings

76
Q

How do you test for protein C deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?

A

Protein C activity (<65%). Reliable in pregnancy. Not reliable during acute thrombosis or on anti-coagulation

77
Q

How do you test for Protein S deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?

A

Function assay (<55%). Not reliable in pregnancy, active thrombosis, or on anti-coagulation. If screening during pregnancy necessary, cutoff values in 2nd and 3rd trimester have been identified at less than 30% and 24% respectively

78
Q

How do you test for antithrombin deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?

A

Antithrombin activity (<60%). Reliable during pregnancy. Not reliable during active thrombus or on anticoagulation

79
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b low-risk thrombophilia without previous VTE?

A

Antepartum: surveillance
Postpartum: Surveillance or prophylactic anticoagulation if additional risk factors

80
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b low-risk thrombophilia with FHx of VTE?

A

Antepartum: Surveillance
Postpartum: Prophylactic anticoagulation or intermediate-dose LMWH/UFH

81
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b low-risk thrombophilia with hx singel prior VTE (not on long term AC)?

A

Antepartum: prophylactic or intermediate-dose LMWH/UFH.
Postpartum: prophlyactic anticoagulation or intermediate-dose LMWH/UFH

82
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b high-risk thrombophilia without previous VTE?

A

Antepartum: prophylactic or intermediate-dose LMWH/UFH
Postpartum: prophylactic AC or intermediate-dose LMWH/UFH

83
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b high-risk thrombophilia w/ one prior VTE or affected 1st degree relative (not on long term AC)?

A

Antepartum: prophylactic, intermediate-dose, or adjusted-dose LMWH/UFH
Postpartum: prophylactic AC, or intermediate or adjusted-dose LMWH/UFH for 6wks

84
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b thrombophilia with two or more episodes of VTE not on long-term AC?

A

Antepartum: Intermediate-dose or adjusted dose LMWH/UFH
Postpartum: Intermediate-dose or adjusted-dose LMWH/UFH for 6wks

85
Q

What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b thrombophilia with 2 or more VTE receiving long-term AC therapy?

A

Antepartum: Adjusted-dose LMWH/UFH
Postpartum: resumption of long-term AC.

86
Q

According to the Anticoagulation Forum, at what % risk of VTE should you start prophylaxis?

A

3% or greater

87
Q

True or false: Women homozygous for factor V Leiden mutation do not need anticoagulation during pregnancy

A

False. Should receive pharmacologic prophylaxis during pregnancy and postpartum

88
Q

True or false: Women homozygous for prothrombin gene mutation need anticoagulation during pregnancy?

A

True. During pregnancy and postpartum

89
Q

Does low-molecular weight heparin cross the placenta?

90
Q

Does unfractionated heparin cross the placenta?

91
Q

In what particular case, could you consider using Vitamin K antagonist during pregnancy?

A

Patient with mechanical heart valve

92
Q

Is low-molecular weight heparin or unfractionated heparin preferred during pregnancy?

A

Low-molecular weight as it has a longer half-life, more predictable dose response, and improved maternal safety profile

93
Q

What is the dosing of prophylactic low molecular weight heparin?

A

Enoxaparin 40mg SC qD.
Dalteparin 5k units SC qD.
Tinzaparin 4.5k units SC qD.
Nadroparin 2.85k units SC qD

94
Q

What is the intermediate-dose LMWH dosing?

A

Enoxaparin 40mg SC q12h.

Dalteparin 5k units SC q12h.

95
Q

What is the adjusted-dose (therapeutic) LMWH dosing? What are target anti Xa levels?

A

Enoxaparin 1mg/kg q12h.
Dalteparin 200 units/kg qD.
Tinzaparin 175 units/kg qD.
Dalteparin 100 units/kg q12h.

Target anti-Xa level 0.6-1 unit/mL 4h after last injection for BID injections, slightly higher for qD.

96
Q

What is the prophylactic unfractionated heparin dosing?

A

UFH 5-7.5k units q15h in first trimester.
UFH 7.5-10k units q12h in second trimester.
UFH 10k units q12h in third trimester unless aPTT elevated

97
Q

What is the adjusted-dose (therapeutic) dosing of UFH?

A

UFH 10k units or more SC q12h, adjusted for target aPTT in range of 1.5-2.5x control 6h after injection

98
Q

When should you initiate anticoagulation for pregnant patients with high risk inherited thrombophilia?

A

Initiate upon confirmation of viable pregnancy

99
Q

Which of the following are compatible with breastfeeding: unfractionated heparin, low-molecular weight heparin, warfarin

A

All are compatible

100
Q

Are oral direct thrombin inhibitors (dabigatran) and anti-Xa inhibitors (rivaroxaban, apixaban) used in pregnancy or breastfeeding?

A

No, insufficient safety data

101
Q

For how long should adjusted-dose low-molecular weight heparin be held prior to induction of labor?

102
Q

For how long should prophylactic low-molecular weight heparin be held prior to induction of labor?

103
Q

How do you reverse unfractionated heparin?

A

Protamine sulfate

104
Q

Can you reverse the anticoagulation effect of low molecular weight heparin?

A

Yes, with protamine sulfate

105
Q

How do doses of postpartum unfractionated heparin and low-molecular weight heparin compare to antepartum therapy?

A

Should be equal

106
Q

When should you start anticoagulation postpartum?

A

Reasonable approach is 4-6 h after vaginal; 6-12h after cesarean

107
Q

What is necessary prior to starting warfarin?

A

Adjusted-dose low-molecular weight heparin or unfractionated heparin bridge until INR is 2.0-3.0 for 2 consecutive days

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