Bleeding Disorders



Bleeding Disorders





The hemostatic system is not completely developed at birth, and this affects normal laboratory ranges and interpretation of bleeding disorders in neonates. There is little evidence to suggest that the immature hemostatic system places neonates at increased risk of hemorrhage. How-ever, in the neonatal period, many hemorrhagic problems appear as a result of the diseases and disorders that occur at that time of life. The study of hemorrhagic disorders in the newborn period requires an understanding of the development of the hemostatic system, of congenital and acquired factors that can affect it, and appreciation of the role of disease in producing disturbances in the system.

Because of the incomplete development of the hemostatic system in neonates, interpretation of laboratory tests in any given infant requires knowledge of normal ranges for healthy infants of similar gestational and postnatal age, as detailed in Tables 46-7 and 46-8 (221). Ideally, each institution should develop their own normal ranges to account for variations that may be caused by the use of different reagents and coagulation analyzers (222). To minimize iatrogenic blood losses associated with multiple


sampling of ill, very low birth weight infants, coagulation laboratories that service neonatal intensive care units (NICUs) should develop microtechniques for the assessment of the hemostatic system (223).








TABLE 46-7 REFERENCE VALUES FOR COAGULATION TESTS IN HEALTHY FULL-TERM INFANTS DURING THE FIRST SIX MONTHS OF LIFE











































































































































































  Day 1 Day 5 Day 30 Day 90 Day 180 Adult
M      B M      B M      B M      B M      B M      B
PT (s) 13.0 (10.1–15.9)* 12.4 (10.0–15.3)*† 11.8 (10.0–14.3)*† 11.9 (10.0–14.2)* 12.3 (10.7–13.9)* 12.4 (10.8–13.9)
INR 1.00 (0.53–1.62) 0.89 (0.53–1.48) 0.79 (0.53–1.26) 0.81 (0.53–1.26) 0.88 (0.61–1.17) 0.89 (0.64–1.17)
APTT (s) 42.9 (31.3–54.5) 42.6 (25.4–59.8) 40.4 (32.0–55.2) 37.1 (29.0–50.1)* 35.5 (28.1–42.9)* 33.5 (26.6–40.3)
TCT (s) 23.5 (19.0–28.3)* 23.1 (18.0–29.2)† 24.3 (19.4–29.2)* 25.1 (20.5–29.7)* 25.5 (19.8–31.2)* 25.0 (19.7–30.3)
Fibrinogen (g/L) 2.83 (1.67–3.99)* 3.12 (1.62–4.62)* 2.70 (1.62–3.78)* 2.43 (1.50–3.87)*† 2.51 (1.50–3.87)*† 2.78 (1.56–4.00)
FII (U/ml) 0.48 (0.26–0.7) 0.63 (0.33–0.93) 0.68 (0.34–1.02) 0.75 (0.45–1.05) 0.88 (0.60–1.16) 1.08 (0.70–1.46)
FV (U/ml) 0.72 (0.34–1.08) 0.95 (0.45–1.45) 0.98 (0.62–1.34) 0.90 (0.45–1.32) 0.91 (0.55–1.27) 1.06 (0.62–1.50)
FVII (U/ml) 0.66 (0.28–1.04) 0.89 (0.35–1.43) 0.90 (0.42–1.38) 0.91 (0.39–1.43) 0.87 (0.47–1.27) 1.05 (0.67–1.43)
FVIII (U/ml) 1.00 (0.50–1.78)*† 0.88 (0.50–1.54)*† 0.91 (0.50–1.57)*† 0.79 (0.50–1.25)*† 0.73 (0.50–1.09)† 0.99 (0.50–1.49)
vWF (U/ml) 1.53 (0.50–2.87)† 1.40 (0.50–2.54)† 1.28 (0.50–2.46)† 1.18 (0.50–2.06)† 1.07 (0.50–1.97)† 0.92 (0.50–1.58)†
FIX (U/ml) 0.53 (0.15–0.91) 0.53 (0.15–0.91) 0.51 (0.21–0.81) 0.67 (0.21–1.13) 0.86 (0.36–1.36) 1.09 (0.55–1.63)
FX (U/ml) 0.40 (0.12–0.68) 0.49 (0.19–0.79) 0.59 (0.31–0.87) 0.71 (0.35–1.07) 0.78 (0.38–1.18) 1.06 (0.70–1.52)
FXI (U/ml) 0.38 (0.10–0.66) 0.55 (0.23–0.87) 0.53 (0.27–0.79) 0.69 (0.41–0.97) 0.86 (0.49–1.34) 0.97 (0.67–1.27)
FXII (U/ml) 0.53 (0.13–0.93) 0.47 (0.11–0.83) 0.49 (0.17–0.81) 0.67 (0.25–1.09) 0.77 (0.39–1.15) 1.08 (0.52–1.64)
PK (U/ml) 0.37 (0.18–0.69)† 0.48 (0.20–0.76) 0.57 (0.23–0.91) 0.73 (0.41–1.05) 0.86 (0.56–1.16) 1.12 (0.62–1.62)
HMWK (U/ml) 0.54 (0.06–1.02) 0.74 (0.16–1.32) 0.77 (0.33–1.21)* 0.82 (0.30–1.46)* 0.82 (0.36–1.28)* 0.92 (0.50–1.36)
FXIIIa (U/ml) 0.79 (0.27–1.31) 0.94 (0.44–1.44)* 0.93 (0.39–1.47)* 1.04 (0.36–1.72)* 1.04 (0.46–1.62)* 1.05 (0.55–1.55)
FXIIIb (U/ml) 0.76 (0.30–1.22) 1.06 (0.32–1.80)* 1.11 (0.39–1.73)* 1.16 (0.48–1.84)* 1.10 (0.50–1.70)* 0.97 (0.57–1.37)
Plasminogen
(CTA U/ml)		 1.95 (1.25–2.65) 2.17 (1.41–2.93) 1.98 (1.26–2.70) 2.48 (1.74–3.22) 3.01 (2.21–3.81) 3.36 (2.48–4.24)
Abbreviations: PT = prothrombin time; s seconds; INR = International Normalized Ratio; APTT = activated partial thromboplastin time; TCT = thrombin clotting time; g/L = grams/litre; F = factor; vWF = von Willebrand factor; PK = prekallikrein; HMWH = high molecular weight kininogen.
All factors except fibrinogen are expressed as units per millilitre (U/ml) where pooled plasma contains 1.0 U/ml. All values are expressed as mean (M) followed by the lower and upper boundary encompassing 95% of the population (B). Between 40 and 77 samples were assayed for each value in each population.
Reproduced with permission from Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns. Semin Perinatol 1997;21:70–85.








TABLE 46-8 REFERENCE VALUES FOR COAGULATION TESTS IN HEALTHY PREMATURE INFANTS (30–36 WEEKS GESTATION) DURING THE FIRST SIX MONTHS OF LIFE



































































































































































  Day 1 Day 5 Day 30 Day 90 Day 180 Adult
M      B M      B M      B M      B M      B M      B
PT (sec) 13.0 (10.6–16.2)* 12.5 (10.0–15.3)*† 11.8 (10.0–13.6)* 12.3 (10.0–14.6)* 12.5 (10.0–15.0)* 12.4 (10.8–13.9)
APTT (sec) 53.6 (27.5–79.4)‡ 50.5 (26.9–74.1)‡ 44.7 (26.9–62.5) 39.5 (28.3–50.7) 37.5 (27.2–53.3)* 33.5 (26.6–40.3)
TCT (sec) 24.8 (19.2–30.4)* 24.1 (18.8–29.4)* 24.4 (18.8–29.9)* 25.1 (19.4–30.8)* 25.2 (18.9–31.5)* 25.0 (19.7–30.3)
Fibrinogen (g/L) 2.43 (1.50–3.73)*†‡ 2.80 (1.60–4.18)*†‡ 2.54 (1.50–4.14)*† 2.46 (1.50–3.52)* 2.28 (1.50–3.60)† 2.78 (1.56–4.00)
FII (U/ml) 0.45 (0.20–0.77)† 0.57 (0.29–0.85)‡ 0.57 (0.36–0.95)†‡ 0.68 (0.30–1.06) 0.87 (0.51–1.23) 1.08 (0.70–1.46)
FV (U/ml) 0.88 (0.41–1.44)*†‡ 1.00 (0.46–1.54)* 1.02 (0.48–1.56) 0.99 (0.59–1.39) 1.02 (0.58–1.46) 1.06 (0.62–1.50)
FVII (U/ml) 0.67 (0.21–1.13) 0.84 (0.30–1.38) 0.83 (0.21–1.45) 0.87 (0.31–1.43) 0.99 (0.47–1.51)* 1.05 (0.67–1.43)
FVIII (U/ml) 1.11 (0.50–2.13)*† 1.15 (0.53–2.05)*†‡ 1.11 (0.50–1.99)*†‡ 1.06 (0.58–1.88)*†‡ 0.99 (0.50–1.87)*†‡ 0.99 (0.50–1.49)
vWF (U/ml) 1.36 (0.78–2.10) † 1.33 (0.72–2.19)† 1.36 (0.66–2.16)† 1.12 (0.75–1.84)*† 0.98 (0.54–1.58)*† 0.92 (0.50–1.58)
FIX (U/ml) 0.35 (0.19–0.65)†‡ 0.42 (0.14–0.74)†‡ 0.44 (0.13–0.80)† 0.59 (0.25–0.93) 0.81 (0.50–1.20)† 1.09 (0.55–1.63)
FX (U/ml) 0.41 (0.11–0.71) 0.51 (0.19–0.83) 0.56 (0.20–0.92) 0.67 (0.35–0.99) 0.77 (0.35–1.19) 1.06 (0.70–1.52)
FXI (U/ml) 0.30 (0.08–0.52)†‡ 0.41 (0.13–0.69)‡ 0.43 (0.15–0.71)‡ 0.59 (0.25–0.93)‡ 0.78 (0.46–1.10) 0.97 (0.67–1.27)
FXII (U/ml) 0.38 (0.10–0.66)‡ 0.39 (0.09–0.69)‡ 0.43 (0.11–0.75) 0.61 (0.15–1.07) 0.82 (0.22–1.42) 1.08 (0.52–1.64)
PK (U/ml) 0.33 (0.09–0.57) 0.45 (0.26–0.75)† 0.59 (0.31–0.87) 0.79 (0.37–1.21) 0.78 (0.40–1.16) 1.12 (0.62–1.62)
HK (U/ml) 0.49 (0.09–0.89) 0.62 (0.24–1.00)‡ 0.64 (0.16–1.12)‡ 0.78 (0.32–1.24) 0.83 (0.41–1.25)* 0.92 (0.50–1.36)
XIIIa (U/ml) 0.70 (0.32–1.08) 1.01 (0.57–1.45)* 0.99 (0.51–1.47)* 1.13 (0.71–1.55)* 1.13 (0.65–1.61)* 1.05 (0.55–1.55)
XIIIb (U/ml) 0.81 (0.35–1.27) 1.10 (0.68–1.58)* 1.07 (0.57–1.57)* 1.21 (0.75–1.67) 1.15 (0.67–1.63) 0.97 (0.57–1.37)
Plasminogen(CTA U/ml) 1.70 (1.12–2.48)‡ 1.91 (1.21–2.61)‡ 1.81 (1.09–2.53) 2.38 (1.58–3.18) 2.75 (1.91–3.59)‡ 3.36 (2.48–4.24)
Abbreviations: PT = Prothrombin time; s = seconds; INR = international normalized ratio; APTT = activated partial thromboplastin time; TCT = thrombin clotting time; g/L = grams per litre; F = Factor; vWF = von Willebrand factor; PK = prekallikrein; HMWK = high molecular weight kininogen.
All factors except fibrinogen are expressed as units per millilitre (U/ml) where pooled plasma contains 1.0 U/ml.
All values are given as means (M) followed by the lower and upper boundary encompassing 95% of the population (B). Between 40 to 96 samples were assayed for each value for the newborn.
* Values that are indistinguishable from those of the adult.
† These measurements are skewed because of a disproportionate number of high values. The lower limit that excludes the lower 2.5% of the population has been given (B). The lower limit for factor VIII was 0.50 U/mL at all points for the infant.
† Values are different from the fullterm infant Reproduced with permission from Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns. Semin Perinatol 1997;21:70–85.

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Jul 1, 2016 | Posted by in OBSTETRICS | Comments Off on Bleeding Disorders

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