#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
2
Q
What obstetric conditions are seen with absent or impair decidua?
A
Ectopic pregnancy and placenta accreta
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
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.
5
Q
Venous thromboembolism complicates x/1,000 pregnancies?
A
0.5-2 per 1,000 pregnancies
6
Q
Venous thromboembolism accounts for what % of pregnancy-related deaths in the US?
A
9.2%
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
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.
9
Q
What is the prevalence (%) of Factor V Leiden heterozygotes in the population?
A
1-15%
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%
11
Q
What is the VTE risk (%) per pregnancy in someone heterozygous for Factor V Leiden in patient with prior VTE?
A
10%
12
Q
Of all cases of VTE during pregnancy, what % occur in women heterozygous for factor V Leiden?
A
40%
13
Q
What is the prevalence (%) of homozygous factor V Leiden?
A
<1%
14
Q
What is the VTE risk per pregnancy (%) in women homozygous for factor V Leiden w/ no prior VTE?
A
2.2-14%
15
Q
What is the VTE risk per pregnancy (%) in women homozygous for factor V Leiden w/ prior VTE?
A
17%
16
Q
Of all cases of VTE during pregnancy, what % occur in women homozygous for factor V Leiden?
A
2%
17
Q
What is the prevalence (%) of prothrombin gene heterozygote?
A
2-5%
18
Q
What is the VTE risk per pregnancy (%) for prothrombin gene heterozygote w/ no prior VTE?
A
0.4-2.6%
19
Q
What is the VTE risk per pregnancy (%) for prothrombin gene heterozygoe w/ prior VTE?
A
> 10%
20
Q
Of all VTE during pregnancy, what % occur in women heterozygous for prothrombin gene?
A
17%
21
Q
What is the prevalence of prothrombin gene homozygote?
A
<1%
22
Q
What is the VTE risk per pregnancy (%) with prothrombin gene homozygote w/ no prior VTE?
A
2-4%
23
Q
What is the VTE risk per pregnancy (%) with prothrombin gene homozygote w/ prior VTE?
A
> 17%
24
Q
Of all VTE during pregnancy, what % occur in women homozygous for prothrombin gene?
A
0.5%
25
What is the prevalence (%) of factor V Leiden/prothrombin gene double heterozygote?
0.01%
26
What is the VTE risk per pregnancy (%) for women with factor V Leiden/prothrombin gene double heterozygote w/ no prior VTE?
4-8.2%
27
What is the VTE risk per pregnancy (%) for women with factor V Leiden/prothrombin gene double heterozygote w/ prior VTE?
>20%
28
Of all VTE during pregnancy, what % occur in double heterozygote for factor V Leiden/prothrombin?
1-3%
29
What is the prevalence (%) of Antithrombin deficiency?
0.02%
30
What is the VTE risk of antithrombin deficiency during pregnancy (%), with no prior VTE?
0.2-11.6%
31
What is the risk of VTE per pregnancy (%) with woman with antithrombin deficiency and prior VTE?
40%
32
Of all VTE during pregnancy, what % occur in women with antithrombin deficiency?
1%
33
What is the prevalence (%) of protein C deficiency?
0.2-0.4%
34
What is the VTE risk per pregnancy (%) in women with protein C deficiency w/ no prior VTE?
0.1-1.7%
35
What is the VTE risk per pregnancy (%) in women with protein C deficiency w/ prior VTE?
4-17%
36
Of all VTE during pregnancy, what % occur in women with protein C deficiency?
14%
37
What is the prevalence of protein S deficiency?
0.03-0.13%
38
What is the VTE risk per pregnancy (%) for women with protein S deficiency and no prior VTE?
0.3-6.6%
39
What is the VTE risk per pregnancy (%) for women with protein S deficiency and prior VTE?
0-22%
40
Of all VTE during pregnancy, what % occur in women with protein S deficiency?
3%
41
What is the prevalence (%) of the factor V Leiden mutation in caucasians, hispanic americans, african americans, asian americans, and native americans?
```
Caucasian - 5.27%
Hispanic american - 2.21%
African american - 1.23%
Asian american - 0.45%
Native american 1.25%
```
42
By what mechanism of action does a mutation in factor V Leiden lead to a prothrombic state?
the mutation renders it refractory to proteoysis by activated protein C.
43
What prothrombin mutation leads commonly leads to a prothrombotic state, what kind of mutation?
Prothrombin G20210A mutation is a point mutation
44
How does the prothrombin G20210A mutation lead to prothrombotic state?
Results in elevated circulating prothrombin levels
45
What is a commonly used cutoff for protein C to be considered abnormal?
A protein C level less than 65% is typically considered abnormal
46
Newborns who are homozygous for protein C can develop what rare condition, how does it present, what treatment is necessary?
Neonatal purpura fulminans, a rare life-threatening condition characterized by disseminated intravascular coagulation and hemorrhagic skin necrosis, and will require lifetime anticoagulation therapy
47
Can you screen for protein S deficiency during pregnancy?
Not reliable, due to fluctuating levels of protein S binding protein during pregnancy
48
Newborns who are homozygous for protein S can develop what rare condition, how does it present, what treatment is necessary?
Neonatal purpura fulminans, a rare life-threatening condition characterized by disseminated intravascular coagulation and hemorrhagic skin necrosis, and will require lifetime anticoagulation therapy
49
Is it possible to have antithrombin deficiency with normal antigen levels?
Yes. Can have mutations that alter structure or function leading to decreased function
50
What is the prevalence of heterozygous antithrombin deficiency in general population?
1 per 2,500
51
In nonpregnant patients, how does the risk of VTE change (fold change) among antithrombin-deficient patients?
Risk increased more than 25-fold
52
How does normal pregnancy affect the levels of antithrombin?
Decreases
53
What is the antithrombin activity level (%) in mild antithrombin deficiency?
Between 70 and 85%
54
What is the risk of VTE in pregnant women with no prior VTE and a mild antithrombin deficiency?
0.2-0.4%
55
What is the risk of VTE in pregnant women with hx of thromboembolism, severe antithrombin deficiency (<60% activity)?
Risk as high as 40%
56
What is the risk of VTE in women with antithrombin deficiency in the anepartum and postpartum period?
Antepartum - 7.3%
| Postpartum 11.1%
57
What is the most common cause of hyperhomocysteinemia?
Homozygosity for the MTHFR (methylenetetrahydrofolate reductase) gene mutation
58
Does MTHFR (methylenetetrahydrofolate reductase) mutations increase risk of VTE?
Does not appear to, in pregnant and non pregnant women
59
What associations are there between inherited thrombophilias and adverse pregnancy outcomes?
No or weak associations between inherited thrombophilias and adverse pregnancy outcomes
60
Do inherited thrombophilias increase the risk of first trimester pregnancy loss?
No
61
What is the recommendation for a women with prior pregnancy loss and inherited thrombophilia?
No anti coagulation. Consider ASA
62
Should inherited thrombophilias be screened for in setting of stillbirth?
No. Only a weak association between Factor V Leiden mutation and stillbirth. No association with prothrombin or MTHFR mutations
63
Is there an association between inherited thrombophilias and preeclampsia?
There is insufficient evidence to conclude that there is an association
64
Is there an association between inherited thrombophilias and fetal growth restriction?
No significant associations
65
Is there an association between inherited thrombophilias and placental abruption?
Insufficient evidence to establish a link between thrombophilias and placental abruption
66
Is anticoagulation recommended to pregnant women with inherited thrombophilias as an intervention to prevent adverse pregnancy outcomes?
Insufficient evidence to recommend anticoagulation for this purpose
67
Would you recommend targeted assessment for inherited thrombophilias for the following patient: Personal hx of VTE, without recurrent risk factor, no prior thrombophilia testing
Yes
68
Would you recommend targeted assessment for inherited thrombophilias for the following patient: Personal hx of VTE, with recurrent risk factor, no prior thrombophilia testing
yes
69
Would you recommend targeted assessment for inherited thrombophilias for the following patient: First-degree relative with a hx of high-risk inherited thrombophilia
Yes
70
Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of fetal loss
No
71
Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of placental abruption
No
72
Would you recommend targeted assessment for inherited thrombophilias for the following patient: Hx of fetal growth restriction
No
73
What are the recommended inherited thrombophilia screening tests for women with personal hx of VTE?
Factor V Leiden mutation, prothrombin G20210A mutation, antithrombin, protein S, and protein C deficiencies
74
How do you test for factor V Leiden mutation? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?
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
How do you test for prothrombin G20210A mutation? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?
DNA analysis. Reliable in all settings
76
How do you test for protein C deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?
Protein C activity (<65%). Reliable in pregnancy. Not reliable during acute thrombosis or on anti-coagulation
77
How do you test for Protein S deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?
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
How do you test for antithrombin deficiency? Is testing reliable during pregnancy? During acute thrombosis? With anti-coagulation?
Antithrombin activity (<60%). Reliable during pregnancy. Not reliable during active thrombus or on anticoagulation
79
What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b low-risk thrombophilia without previous VTE?
Antepartum: surveillance
Postpartum: Surveillance or prophylactic anticoagulation if additional risk factors
80
What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b low-risk thrombophilia with FHx of VTE?
Antepartum: Surveillance
Postpartum: Prophylactic anticoagulation or intermediate-dose LMWH/UFH
81
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)?
Antepartum: prophylactic or intermediate-dose LMWH/UFH.
Postpartum: prophlyactic anticoagulation or intermediate-dose LMWH/UFH
82
What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b high-risk thrombophilia without previous VTE?
Antepartum: prophylactic or intermediate-dose LMWH/UFH
Postpartum: prophylactic AC or intermediate-dose LMWH/UFH
83
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)?
Antepartum: prophylactic, intermediate-dose, or adjusted-dose LMWH/UFH
Postpartum: prophylactic AC, or intermediate or adjusted-dose LMWH/UFH for 6wks
84
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?
Antepartum: Intermediate-dose or adjusted dose LMWH/UFH
Postpartum: Intermediate-dose or adjusted-dose LMWH/UFH for 6wks
85
What is the recommended thromboprophylaxis (antepartum and postpartum) for pregnancies c/b thrombophilia with 2 or more VTE receiving long-term AC therapy?
Antepartum: Adjusted-dose LMWH/UFH
Postpartum: resumption of long-term AC.
86
According to the Anticoagulation Forum, at what % risk of VTE should you start prophylaxis?
3% or greater
87
True or false: Women homozygous for factor V Leiden mutation do not need anticoagulation during pregnancy
False. Should receive pharmacologic prophylaxis during pregnancy and postpartum
88
True or false: Women homozygous for prothrombin gene mutation need anticoagulation during pregnancy?
True. During pregnancy and postpartum
89
Does low-molecular weight heparin cross the placenta?
No
90
Does unfractionated heparin cross the placenta?
No
91
In what particular case, could you consider using Vitamin K antagonist during pregnancy?
Patient with mechanical heart valve
92
Is low-molecular weight heparin or unfractionated heparin preferred during pregnancy?
Low-molecular weight as it has a longer half-life, more predictable dose response, and improved maternal safety profile
93
What is the dosing of prophylactic low molecular weight heparin?
Enoxaparin 40mg SC qD.
Dalteparin 5k units SC qD.
Tinzaparin 4.5k units SC qD.
Nadroparin 2.85k units SC qD
94
What is the intermediate-dose LMWH dosing?
Enoxaparin 40mg SC q12h.
| Dalteparin 5k units SC q12h.
95
What is the adjusted-dose (therapeutic) LMWH dosing? What are target anti Xa levels?
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
What is the prophylactic unfractionated heparin dosing?
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
What is the adjusted-dose (therapeutic) dosing of UFH?
UFH 10k units or more SC q12h, adjusted for target aPTT in range of 1.5-2.5x control 6h after injection
98
When should you initiate anticoagulation for pregnant patients with high risk inherited thrombophilia?
Initiate upon confirmation of viable pregnancy
99
Which of the following are compatible with breastfeeding: unfractionated heparin, low-molecular weight heparin, warfarin
All are compatible
100
Are oral direct thrombin inhibitors (dabigatran) and anti-Xa inhibitors (rivaroxaban, apixaban) used in pregnancy or breastfeeding?
No, insufficient safety data
101
For how long should adjusted-dose low-molecular weight heparin be held prior to induction of labor?
24 hours
102
For how long should prophylactic low-molecular weight heparin be held prior to induction of labor?
12 hours
103
How do you reverse unfractionated heparin?
Protamine sulfate
104
Can you reverse the anticoagulation effect of low molecular weight heparin?
Yes, with protamine sulfate
105
How do doses of postpartum unfractionated heparin and low-molecular weight heparin compare to antepartum therapy?
Should be equal
106
When should you start anticoagulation postpartum?
Reasonable approach is 4-6 h after vaginal; 6-12h after cesarean
107
What is necessary prior to starting warfarin?
Adjusted-dose low-molecular weight heparin or unfractionated heparin bridge until INR is 2.0-3.0 for 2 consecutive days
