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Thrombophilia risk is not increased in children after perinatal stroke

Colleen Curtis, Aleksandra Mineyko, Patricia Massicotte, Michael Leaker, Xiu Yan Jiang, Amalia Floer and Adam Kirton
This article has an Erratum 130(3):382

Article Figures & Data

Figures

  • Figure 1.

    Comparison by number of prothrombotic abnormalities. Relative proportions of participants having each of none through 6 abnormalities are shown by stroke group or controls. Most participants had no abnormalities. No difference was found between stroke groups and controls regardless of number of abnormalities.

Tables

  • Table 1.

    Population characteristics

    NAISAPPISPVIControl
    Number46345577
    Male (%)28 (61)14 (41)36 (65)45 (58)
    Median age (range), years1.8 (0.8-17.9)10.3 (0.8-17.9)6.5 (0.9-19.1)5.4 (0.9-17.6)
    • The final sample size, sex, and distributions are shown for the perinatal stroke populations of NAIS, APPIS, and PVI and controls. Groups were comparable, except median age in the NAIS group was lower.

  • Table 2.

    Normative control values

    MeanStandard error95% CILaboratory reference range
    PT, s11.90.1010.6-13.510.2-13.1
    INR1.10.011.0-1.20.9-1.1
    PTT, s32.80.5828.3-37.527.0-37.0
    Fibrinogen, g/L2.40.061.7-3.31.4-4.1
    Antithrombin, U/mL1.030.0130.86-1.210.078-1.24
    Protein C activity, U/mL0.870.0250.52-1.270.67-1.26
    Protein S activity, U/mL0.870.0190.64-1.110.71-1.42
    Protein S free, U/mL0.830.0160.63-1.100.65-1.22
    Factor VIII, U/mL1.000.0340.60-1.530.54-1.47
    Factor IX, U/mL0.760.0180.54-1.070.55-1.6
    Factor XI, U/mL1.150.0320.77-1.570.55-1.38
    Lp(a), g/L0.230.0390.00-0.73<0.3
    • Mean, variance, and 95% confidence intervals are shown for all quantified variables. Existing reference ranges from our laboratory based on testing in adolescents and adults are provided for comparison

    • INR, international normalized ratio; PT, prothrombin time; PTT, partial thromboplastin time.

  • Table 3.

    Quantified prothrombotic factor group comparisons

    PVIAISControlP
    MeanSE95% CIMeanSE95% CIMeanSE95% CI
    PT, s11.80.1210.3-13.311.30.0910.1-12.611.90.1010.6-13.5<.001*
    INR1.00.010.9-1.11.00.010.9-1.11.10.011.0-1.2<.001*
    PTT, s31.90.4227.9-37.731.60.3927.1-38.032.80.5828.3-37.5.18
    Fibrinogen, g/L2.50.071.8-3.32.50.071.7-3.82.40.061.7-3.3.51
    Antithrombin, U/mL1.060.0200.88-1.281.090.0160.86-1.301.030.0130.86-1.21.018*
    Protein C, U/mL0.870.0270.63-1.240.870.0250.51-1.220.870.0250.52-1.27.99
    Protein S activity, U/mL0.850.0220.57-1.130.860.0200.60-1.200.870.0190.64-1.11.83
    Protein S free, U/mL0.860.0210.60-1.100.850.0180.55-1.090.830.0160.63-1.10.48
    Factor VIII, U/mL1.040.0460.58-1.691.000.0320.64-1.471.000.0340.60-1.53.72
    Factor IX, U/mL0.770.0180.60-1.010.800.0230.54-1.170.760.0180.54-1.07.32
    Factor XI, U/mL1.000.0370.62-1.391.020.0330.69-1.581.150.0320.77-1.57.004*
    Lp(a), g/L0.240.0400.00-0.690.240.0370.00-0.910.230.0390.00-0.73.989
    • Mean, standard error, and 95% CI for each continuous variable outcome are shown for PIV, AIS (comprising NAIS and APPIS), and controls. P value reflects significance of the original analysis of variance without correction for multiple comparisons.

    • INR, international normalized ratio; PT prothrombin time; PTT partial thromboplastin time.

    • * Significant pairwise difference.

  • Table 4.

    Frequency of abnormal results across groups

    No. (%)
    PVIAISControl
    PT1 (2)4 (5)1 (1)
    INR01 (1)0
    PTT4 (8)6 (8)3 (4)
    Fibrinogen01 (1)0
    Antithrombin01 (1)1 (1)
    Protein C5 (10)7 (9)10 (14)
    Protein S9 (18)9 (12)10 (14)
    Protein S free9 (17)12 (16)18 (24)
    Factor VIII4 (8)4 (6)5 (7)
    Factor IX000
    Factor XI3 (6)8 (11)12 (16)
    Lp(a)000
    Anticardiolipin antibody*5 (10)7 (10)2 (3)
    Lupus inhibitor001 (1)
    • Using the established normative values and direction of abnormality favoring thrombophilia, the proportion of participants with abnormal results are shown. No differences were observed between groups, including individual analysis of NAIS and APPIS populations.

    • INR, international normalized ratio; PT prothrombin time; PTT partial thromboplastin time.

    • * Anticardiolipin results shown are from the original test and were normal on repeat testing in 86%.

  • Table 5.

    Thrombophilia genotypes

    PVINAISAPPISArterialPopulation
    FVL
     Heterozygous5336
     Homozygous1000
     Wild type49433275
     Mutation, %10.76.38.17.26
     95% CI1.5-16.7−0.7-17.9−0.7-17.81.70-13.1
    Prothrombin 20210A
     Heterozygous3112
     Wild type52453479
     Mutation, %5.42.22.92.43.8
     95% CI−0.55-11.5−2.0-6.4−2.6-8.4−0.91-5.85
    MTHFR
     Homozygous TT6437
      Mutation, %11.79.39.19.2*15
      95% CI2.92-20.60.62-18.0−0.7-18.92.7-15.7
     Heterozygous CT21161329
      Mutation, %41.137.239.338.137
      95% CI27.6-54.722.8-51.722.7-56.127.2-49.1
     Homozygous CC24231740
      Mutation, %4753.451.552.657
      95% CI33.4-60.838.6-68.434.4-68.641.4-63.9
    • Proportions of each genotype for FVL, prothrombin gene 20210A, and MTHFR are shown for each perinatal stroke disease. Control prevalence is estimated from the literature. No differences were observed between groups except all arterial had significantly lower occurrence of the TT genotype (P = .04). Ten patients (PVI, 5; NAIS, 3; APPIS, 2) did not have MTHFR results available. Homocysteine levels did not differ by stroke group or genotype.

    • * P = .04, all arterial lower than PVI.