THROMBOSIS RESEARCH Printed in the United
LETTER
vol. States
TO THE
6,
pp. 201-202, Pergamon Press,
1975 Inc.
EDITORS-IN-CHIEF
A PECULIAR HAEMOSTATICMECHANISMIN THE RAT?
G.de Gaetano,M.B.Donati,A.Poggi I.Reyers-Degli Innocenti and ti.C.Roncaglioni Laboratory for Haemostasis and Thrombosis Research Istituto di Ricerche Farmacologiche ‘Mario Negri’ Via Eritrea, 62 - 20157 MILAN, Italy
(Received
in revised 27.11.1974; Accepted by Editor A.L.
form 30.12.1974. Copley)
Recent work performed in our laboratory(l) has shown that platelets from normal rats of 3 different strains are refractory botn in vitro and in vivo to aggregation induced by ristocetin and by iJillebrand fact-different origin (bovine,porcine, and upon previous treatment with neuraminidase) . human, the latter Since a plasmatic defect could be excluded, on the basis of crossed experiments, we have suggested that rat platelet membrane may lack a receptor (sialic acid? sialyltransferase?) necessary for its interaction with ristocetin and heterologous Willebrand factors. This anomaly is very similar to that recently described in some patients with giant platelet (Bernard-Soulier) syndrome(2); the rats we have studied however, did not suffer from any manifest haemorrhagic diathesis so that the significance of our laboratory . findings for the haemostasis of rat remains to be established Besides unresponsiveness to ristocetin and Willebrand factors, rat platelets have been described to possess several other peculiarities: indeed they adhere to tendon suspension (3), to collagen(l) and to glass beads (4) less readily than human platelets. In his recent editorial (5) Copley refers to a paper by Apitz and Hiihn(6) indicating that in rat possibly less than 10,000 platelets/u1 are sufficient for the formation of wound thrombi ; these authors concluded that the haemostatic defects in human thrombocytopenia must have other causes than the marked diminution in the platelet count . Although we agree that the problem of haemostasis in man may not mainly or necessarily depend on we would caution investigators to extrapolate to platelets (5), human haemostasis the results obtained in rat, an animal species whose haemostasis is possibly quite peculiar . Very recently, Thilo and BGhm (7) have reported that,immediately after a standardized injury of the abdominal rat skin, a great amount of red cells and only very few platelet aggregates can be 201
202
HEMOSTASIS IN THE RAT
vol. ~,No.~ 2
seen in the area of bleeding, interwoven with fibrin-like material; these authors have suggested that primary bleeding may be terminated by accumulation of red cells rather than of platelets with subsequent rapid formation of fibrin-like material. This material may well be polymerized fibrinogen adsorbed layer upon layer at the site of the vessel wound, according to the original concept on the mechanisms of haemostasis developed by Copley in his Editorial (5) . Intriguing enough, we have recently observed(8) that infusion of AUP into rats provokes a transient platelet aggregation and a sustained haemolysis, the two phenomena being largely independent from one another . These results emphasize that the relative contribution of platelets , red cells, fibrinogen and possibly other plasma proteins in the haemostatic mechanism of rat deserves further investigation . REFERENCES
1) de GAETANO G., DONATI M.B., REYERS-DEGLI INNOCENTI I., and
M.C. : In vitro and In vivo absence of rat platelet aggregation by both heterologous high molecular weight factor VIII-related material and ristocetin.Circulation -5~ , Supplement 3,282(1974). CAEN J.P.,LEVY-TOLEDANO S.,SULTAM Y.and BERNARD J.:La distrophie thrombocytaire h6morragipare(interaction des plaquettes et du facteur Willebrand).Nouv.Kev.Franc.H~mat.l3:S95(1973). 3) CONSTANTINE J.A,:Aggregation and adhesion of rat platelets: Nature(Lond.) 214 : 1084 (1967) . RONCAGLIONI
4) NORDOY A. and ODEGAARD A.H.:The influence of citrate and heparin on the adhesiveness or rat platelets and human platelets measured in vitro. Scand.J.Clin.Lab.Invest. 15 : 399 (1963). 3) COPLEY A.L. : Bleeding time, other in vivo hemostasis tests and the arrest of hemorrhage. Thrombos.Res. 4: 1 (1974) . 6) APITZ K., and Hiihn U.: Uber die Thrombopenie bei Benzolvergiftung der Ratte. Ztschr.ges.exp.bled. 111 : 540 (1942) in haemostasis. 7) THILO D. and BOHM E. : A 3-S second DhenOmenOn A scanning electron microscopic stud~.Thrombos.Diathes.haemorrh. . \ -30 : 363 (19731 8) REYERS-DEGLI INNOCENT1 I., POGGI A. and de GAETANO G. : Platelet aggregation and haemolysis induced in rats by intravenous infusion of adenosine diphosphate. Effect of potentially antithrombotic drugs. Scand,J. Haemat. in the press . I
LETTER
vol. States
TO THE
6,
pp. 201-202, Pergamon Press,
1975 Inc.
EDITORS-IN-CHIEF
A PECULIAR HAEMOSTATICMECHANISMIN THE RAT?
G.de Gaetano,M.B.Donati,A.Poggi I.Reyers-Degli Innocenti and ti.C.Roncaglioni Laboratory for Haemostasis and Thrombosis Research Istituto di Ricerche Farmacologiche ‘Mario Negri’ Via Eritrea, 62 - 20157 MILAN, Italy
(Received
in revised 27.11.1974; Accepted by Editor A.L.
form 30.12.1974. Copley)
Recent work performed in our laboratory(l) has shown that platelets from normal rats of 3 different strains are refractory botn in vitro and in vivo to aggregation induced by ristocetin and by iJillebrand fact-different origin (bovine,porcine, and upon previous treatment with neuraminidase) . human, the latter Since a plasmatic defect could be excluded, on the basis of crossed experiments, we have suggested that rat platelet membrane may lack a receptor (sialic acid? sialyltransferase?) necessary for its interaction with ristocetin and heterologous Willebrand factors. This anomaly is very similar to that recently described in some patients with giant platelet (Bernard-Soulier) syndrome(2); the rats we have studied however, did not suffer from any manifest haemorrhagic diathesis so that the significance of our laboratory . findings for the haemostasis of rat remains to be established Besides unresponsiveness to ristocetin and Willebrand factors, rat platelets have been described to possess several other peculiarities: indeed they adhere to tendon suspension (3), to collagen(l) and to glass beads (4) less readily than human platelets. In his recent editorial (5) Copley refers to a paper by Apitz and Hiihn(6) indicating that in rat possibly less than 10,000 platelets/u1 are sufficient for the formation of wound thrombi ; these authors concluded that the haemostatic defects in human thrombocytopenia must have other causes than the marked diminution in the platelet count . Although we agree that the problem of haemostasis in man may not mainly or necessarily depend on we would caution investigators to extrapolate to platelets (5), human haemostasis the results obtained in rat, an animal species whose haemostasis is possibly quite peculiar . Very recently, Thilo and BGhm (7) have reported that,immediately after a standardized injury of the abdominal rat skin, a great amount of red cells and only very few platelet aggregates can be 201
202
HEMOSTASIS IN THE RAT
vol. ~,No.~ 2
seen in the area of bleeding, interwoven with fibrin-like material; these authors have suggested that primary bleeding may be terminated by accumulation of red cells rather than of platelets with subsequent rapid formation of fibrin-like material. This material may well be polymerized fibrinogen adsorbed layer upon layer at the site of the vessel wound, according to the original concept on the mechanisms of haemostasis developed by Copley in his Editorial (5) . Intriguing enough, we have recently observed(8) that infusion of AUP into rats provokes a transient platelet aggregation and a sustained haemolysis, the two phenomena being largely independent from one another . These results emphasize that the relative contribution of platelets , red cells, fibrinogen and possibly other plasma proteins in the haemostatic mechanism of rat deserves further investigation . REFERENCES
1) de GAETANO G., DONATI M.B., REYERS-DEGLI INNOCENTI I., and
M.C. : In vitro and In vivo absence of rat platelet aggregation by both heterologous high molecular weight factor VIII-related material and ristocetin.Circulation -5~ , Supplement 3,282(1974). CAEN J.P.,LEVY-TOLEDANO S.,SULTAM Y.and BERNARD J.:La distrophie thrombocytaire h6morragipare(interaction des plaquettes et du facteur Willebrand).Nouv.Kev.Franc.H~mat.l3:S95(1973). 3) CONSTANTINE J.A,:Aggregation and adhesion of rat platelets: Nature(Lond.) 214 : 1084 (1967) . RONCAGLIONI
4) NORDOY A. and ODEGAARD A.H.:The influence of citrate and heparin on the adhesiveness or rat platelets and human platelets measured in vitro. Scand.J.Clin.Lab.Invest. 15 : 399 (1963). 3) COPLEY A.L. : Bleeding time, other in vivo hemostasis tests and the arrest of hemorrhage. Thrombos.Res. 4: 1 (1974) . 6) APITZ K., and Hiihn U.: Uber die Thrombopenie bei Benzolvergiftung der Ratte. Ztschr.ges.exp.bled. 111 : 540 (1942) in haemostasis. 7) THILO D. and BOHM E. : A 3-S second DhenOmenOn A scanning electron microscopic stud~.Thrombos.Diathes.haemorrh. . \ -30 : 363 (19731 8) REYERS-DEGLI INNOCENT1 I., POGGI A. and de GAETANO G. : Platelet aggregation and haemolysis induced in rats by intravenous infusion of adenosine diphosphate. Effect of potentially antithrombotic drugs. Scand,J. Haemat. in the press . I
