Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony‐stimulating factor

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

Section: Discussionmentioning

confidence: 99%

Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination

Söhngen

Wienen

Siebler

et al. 1998

“…No serious consequences attributable to giving G-CSF have been identified in the early years after BC donation; this is consistent with most other reports, although severe effects have been described. [30][31][32] Information from this study is now incorporated into our standard teaching brochure to educate future donors about the potential side effects and expected recovery time with each procedure. This includes a recommendation about the effective contraception in women of childbearing age.…”

Section: Discussionmentioning

confidence: 99%

Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue

Karlsson¹,

Quinlan²,

Guo³

et al. 2004

Summary:This prospective study compared the donor experience of blood cell (BC) mobilization and leukapheresis (n ¼ 116) with that of bone marrow (BM) harvest (n ¼ 55). Internal jugular catheters were inserted electively in 89% of BC donors. Most (80%) BM donors had a harvest with general anesthesia; 20% had epidural or spinal anesthesia. Pain and fatigue were frequent with both procedures and were compared in responses to questionnaires. A total of 85% of BM donors reported moderate or severe pain compared with 68% of BC donors (P ¼ 0.02). The median duration of pain was 14 days for BM donors compared with 3 days after BC mobilization (Po0.0001). More BM donors had pain for more than 7 days (75% vs 0%, Po0.0001). Severe fatigue was experienced by more BM donors (49 vs 16%, Po0.0001). Fatigue lasted significantly longer in BM donors (median 11 vs 4 days, Po0.0001) and more BM donors were fatigued for more than 1 week (69 vs 0%, Po0.0001). A total of 11 donors had both BM and BC collection; seven preferred the latter. Simply considered with respect to pain and fatigue, BC donation appears better tolerated by donors. However, there are other sequelae of both influencing the acceptability for individual donors.

“…The authors assumed that hyperleukocytosis (leukocyte count of 70.5 × 10 9 /l) induced by G-CSF, with a presumably subsequent hypercoagulable state, was a contributing factor for the occurrence of thrombosis. In 1996, Kawachi et al 13 reported the case of a 44-year-old man with a non-Hodgkin's lymphoma, who presented with an acute thrombosis in the distal aorta. He was receiving G-CSF for chemotherapy-induced neutropenia and had no predisposing cardiovascular factors.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of G-CSF effects on hemostasis in allogeneic blood stem cell donors

LeBlanc

Roy

Demers

et al. 1999

Summary:Granulocyte colony-stimulating factor (G-CSF) is used in healthy donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. However, some data have recently suggested that G-CSF may induce a hypercoagulable state, prompting us to study prospectively 22 PBSC donors before and after G-CSF 5 g/kg twice daily. We sought evidence for changes in the following parameters: platelet count, von Willebrand factor antigen (vWF:Ag) and activity (vWF activity), ␤-thromboglobulin (␤-TG), platelet factor 4 (PF-4), platelet activation markers (GMP-140 and PAC-1), activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulant factor VIII (FVIII:C), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), thrombomodulin (TM) and tissue plasminogen activator antigen (tPA:Ag) prior to G-CSF and immediately before leukapheresis. ADP-induced platelet aggregation studies were also performed. G-CSF administration produced only mild discomfort. We found a significant increase in vWF:Ag (from 0.99 ؎ 0.32 U/ml to 1.83 ؎ 0.69 U/ml; P Ͻ 0.001), in vWF activity (from 1.04 ؎ 0.34 U/ml to 1.78 ؎ 0.50 U/ml; P Ͻ 0.001) and in FVIII:C (from 1.12 ؎ 0.37 U/ml to 1.73 ؎ 0.57 U/ml; P Ͻ 0.001) after G-CSF. Of note, four donors with low baseline vWF had a two-to three-fold increase after receiving G-CSF. G-CSF had no impact on the platelet count, ␤-TG, PF-4, GMP-140 or PAC-1. The final% of platelet aggregation decreased from 73 ؎ 22% to 37 ؎ 26% after G-CSF (P Ͻ 0.001). We found a significant decrease in aPTT after G-CSF (29.9 ؎ 3.1 s to 28.3 ؎ 3.3 s; P = 0.004), but the PT was unaffected. In addition, we also observed a significant increase in TAT, F1+2 and TM, but not in tPA:Ag. Our data suggest that G-CSF may possibly induce a hypercoagulable state by increasing levels of FVIII:C and thrombin generation. In contrast to this information, we found reduced platelet aggregation after G-CSF administration. The clinical implications of these findings remain unclear and larger studies are definitely required.