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Pregnancy complications in acquired thrombotic thrombocytopenic purpura: a case-control study.

Ferrari B, Maino A, Lotta LA, Artoni A, Pontiggia S, Trisolini SM, Malato A, Rosendaal FR, Peyvandi F - Orphanet J Rare Dis (2014)

Bottom Line: However, the exact entity of these risks and their causes are unknown.In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies.ADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

View Article: PubMed Central - PubMed

Affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy. barbara.ferrari@policlinico.mi.it.

ABSTRACT

Background: Pregnant women with a history of acquired thrombotic thrombocytopenic purpura (TTP) are considered at risk for disease recurrence and might be at risk for miscarriage, similar to other autoimmune disorders. However, the exact entity of these risks and their causes are unknown. The aim of this study was to evaluate risk factors associated with adverse pregnancy outcome, in terms of both gravidic TTP and miscarriage, in women affected by previous acquired TTP.

Methods: We conducted a nested case-control study in women with a history of acquired TTP enrolled in the Milan TTP registry from 1994 to October 2012, with strict inclusion criteria to reduce referral and selection bias.

Results: Fifteen out of 254 women with acquired TTP were included, namely four cases with gravidic TTP, five with miscarriage, and six controls with uncomplicated pregnancy. In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies. Reduced levels of ADAMTS13 activity (<25%) in the first trimester were associated with an over 2.9-fold increased risk for gravidic TTP and with an over 1.2-fold increased risk for miscarriage (lower boundary of the confidence interval of the odds ratio). In addition, the presence of anti-ADAMTS13 antibodies during pregnancy was associated with an over 6.6-fold increased risk for gravidic TTP and with an over 4.1-fold increased risk for miscarriage.

Conclusions: ADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

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Related in: MedlinePlus

Study flow-chart for women selection.Abbreviations: TTP, Thrombotic thrombocytopenic purpura.
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Fig1: Study flow-chart for women selection.Abbreviations: TTP, Thrombotic thrombocytopenic purpura.

Mentions: At the moment of the closing of the database (October 2012), the Milan TTP Registry included 254 women with acquired TTP; of those, 17 met the strict inclusion criteria of this study. One patient was excluded because of pregnancy termination (reason unrelated to TTP) and another one was excluded due to a history of cancer-associated recurrent TTP. Therefore 15 women were included in the analysis (Figure 1). Their main clinical characteristics (age at pregnancy, gravidity, pregnancy outcome and duration, number of previous episodes of TTP) are reported in Table 1, while ADAMTS13-related measurements are reported in Table 2. All women were Caucasian; median age at pregnancy was 32 years (range 24–38 years) and 9 were primigravidae; 6 had a history of recurrent TTP; the median time between the previous TTP episode and conception was 28 months (range 2–107 months). All patients were affected by autoimmune TTP (detectable anti-ADAMTS13 antibodies at least once in the patient’s history, before inclusion in the study); in all women except patient 11, severe ADAMTS13 deficiency (i.e., <10%) was detected in either acute or remission phase, out of pregnancy.Figure 1


Pregnancy complications in acquired thrombotic thrombocytopenic purpura: a case-control study.

Ferrari B, Maino A, Lotta LA, Artoni A, Pontiggia S, Trisolini SM, Malato A, Rosendaal FR, Peyvandi F - Orphanet J Rare Dis (2014)

Study flow-chart for women selection.Abbreviations: TTP, Thrombotic thrombocytopenic purpura.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4279798&req=5

Fig1: Study flow-chart for women selection.Abbreviations: TTP, Thrombotic thrombocytopenic purpura.
Mentions: At the moment of the closing of the database (October 2012), the Milan TTP Registry included 254 women with acquired TTP; of those, 17 met the strict inclusion criteria of this study. One patient was excluded because of pregnancy termination (reason unrelated to TTP) and another one was excluded due to a history of cancer-associated recurrent TTP. Therefore 15 women were included in the analysis (Figure 1). Their main clinical characteristics (age at pregnancy, gravidity, pregnancy outcome and duration, number of previous episodes of TTP) are reported in Table 1, while ADAMTS13-related measurements are reported in Table 2. All women were Caucasian; median age at pregnancy was 32 years (range 24–38 years) and 9 were primigravidae; 6 had a history of recurrent TTP; the median time between the previous TTP episode and conception was 28 months (range 2–107 months). All patients were affected by autoimmune TTP (detectable anti-ADAMTS13 antibodies at least once in the patient’s history, before inclusion in the study); in all women except patient 11, severe ADAMTS13 deficiency (i.e., <10%) was detected in either acute or remission phase, out of pregnancy.Figure 1

Bottom Line: However, the exact entity of these risks and their causes are unknown.In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies.ADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

View Article: PubMed Central - PubMed

Affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy. barbara.ferrari@policlinico.mi.it.

ABSTRACT

Background: Pregnant women with a history of acquired thrombotic thrombocytopenic purpura (TTP) are considered at risk for disease recurrence and might be at risk for miscarriage, similar to other autoimmune disorders. However, the exact entity of these risks and their causes are unknown. The aim of this study was to evaluate risk factors associated with adverse pregnancy outcome, in terms of both gravidic TTP and miscarriage, in women affected by previous acquired TTP.

Methods: We conducted a nested case-control study in women with a history of acquired TTP enrolled in the Milan TTP registry from 1994 to October 2012, with strict inclusion criteria to reduce referral and selection bias.

Results: Fifteen out of 254 women with acquired TTP were included, namely four cases with gravidic TTP, five with miscarriage, and six controls with uncomplicated pregnancy. In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies. Reduced levels of ADAMTS13 activity (<25%) in the first trimester were associated with an over 2.9-fold increased risk for gravidic TTP and with an over 1.2-fold increased risk for miscarriage (lower boundary of the confidence interval of the odds ratio). In addition, the presence of anti-ADAMTS13 antibodies during pregnancy was associated with an over 6.6-fold increased risk for gravidic TTP and with an over 4.1-fold increased risk for miscarriage.

Conclusions: ADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

Show MeSH
Related in: MedlinePlus