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Fibrin formation, fibrinopeptide A release, and platelet thrombus
dimensions on subendothelium exposed to flowing native blood: greater in
factor XII and XI than in factor VIII and IX deficiency
HJ Weiss, VT Turitto, WJ Vicic and HR Baumgartner
Fibrin deposition and platelet thrombus dimensions on subendothelium were
studied in four groups of patients with coagulation factor deficiencies.
Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three
patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe
bleeders, whereas four patients with factor XII deficiency and seven with
factor XI deficiency were either asymptomatic or only mild bleeders despite
APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted
segments of deendothelialized rabbit aorta were exposed at a shear rate of
650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular
chamber. Blood coagulation was evaluated by measuring fibrin deposition
(percent surface coverage) on the subendothelium and post-chamber
fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium
were evaluated by determining the total thrombus volume per surface area
(using an optical scanning technique) and the average height of the three
tallest thrombi. Consistent differences were observed among the patient
groups for both the 5-min and 10-min exposure times. The larger of the 5-
and 10-min exposure-time values was used to calculate group averages.
Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and
post- chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly
decreased fibrin deposition and fibrinopeptide A levels were observed in
factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX
deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly
higher values were obtained in patients deficient in factor XI (33% +/- 5%
and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml).
Differences in thrombus dimensions were also observed. In normal subjects,
the value for thrombus volume and average height of the tallest thrombi
were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively,
and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5
+/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/-
3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient
with fibrinogen deficiency, indicating that the smaller thrombi in factor
VIII and factor IX deficiencies were probably due to impaired evolution of
thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400
WORDS)
Volume 63,
Issue 5,
pp. 1004-1014,
05/01/1984
Copyright © 1984 by The American Society of Hematology
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