Summary:Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen. Keywords: in vitro bleeding test; blood coagulation; recombinant human granulocyte colony-stimulating factor; transcranial Doppler ultrasound In the context of autologous and allogeneic stem cell transplantation rhG-CSF is routinely used as a growth factor to mobilize peripheral blood stem cells. 1,2 In patients with normal bone marrow function this leads to a significant increase of peripheral leukocyte counts, so that rheological changes and disturbances of blood flow are to be anticipated. To date, we have noted thrombotic complications of central venous lines in two out of 20 patients under rhG-CSF administration. Moreover, in vitro tests demonstrated an activation of platelets and the coagulation system. 3,4 As a growing number of healthy donors receive rhG-CSF for stem cell mobilization in our institution, we were interested
The effects of platelet counts, hematocrit, and leukocyte counts were studied on the closure times of the Thrombostat 4000 (in-vitro bleeding time, IVBT). Closure times became longer with platelet counts <50 x 10'!L; an inverse linear correlation could be established. Hematocrit was also inversely correlated with the closure time. At constant platelet counts a hematocrit of 55% yielded an immediate closure of the filter, while with a hematocrit <15% no closure times could be measured. At constant platelet counts and hematocrits, nomonuclear and polymorphonuclear leukocytes also inDuenced closure times; increased counts resulted in shorter closure times. Leukocytes from a patient with chronic myelocytic leukemia had the same effects.
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