Hematin is clinically useful in the treatment of
acute intermittent porphyria. Recently,
hematin-induced coagulopathy has been reported, and a patient we treated bled during
hematin therapy. On 3 separate occasions, infusions of
hematin (4 mg/kg) induced
thrombocytopenia, prolongation of the prothrombin time, partial thromboplastin time. Reptilase time, and apparent decreases in
fibrinogen and increases in
fibrin(
ogen) degradation products (
FDP). However,
fibrinogen assayed by heat precipitation was unchanged, the
protamine paracoagulation test was negative, there was no red blood cell fragmentation, and
plasminogen and
antithrombin III remained normal, excluding the presence of
disseminated intravascular coagulation. Furthermore,
premedication with
heparin, 5000 U i.v., failed to prevent the lengthening of the Reptilase time and exacerbated the
thrombocytopenia. In vitro studies revealed that
hematin, 0.1 mg/ml, aggregated platelets and induced the release of 14C-serotonin and
adenosine triphosphate (
ATP).
Hematin also aggregated washed or gel-filtered platelets but had no effect on
formalin-fixed platelets. Aggregation was inhibited by
aspirin (0.12 mg/ml),
adenosine triphosphate, and
apyrase, suggesting that
hematin aggregated platelets by inducing
adenosine diphosphate (
ADP) release.
Hematin (0.07 mg/ml) progressively inactivated
thrombin and 0.1 mg/ml prolonged the Reptilase time. Thus,
hematin is unique in that it both induces platelet aggregation and inhibits coagulation.