Evelyn M. Ross

Simultaneous Fibrinogen and Platelet’ Survival with [75Se]Selenomethionine in Man

Summary. Simultaneous fibrinogen and platelet survivals were determined with a cohort label, [75Se]selenomethionine, in patients with hepatocellular disease and abnormal serial thrombin times (STT) and in control patients. The fibrinogen survival curves were divided into an anabolic and catabolic phase. In a control group maximum labelling of fibrinogen (anabolic phase) occurred within 24 hr and mean fibrinogen survival (catabolic phase) was 7.8 ± 2.8 days. Patients with hepatocellular disease fell into two groups, those with short fibrinogen survivals and those with normal fibrinogen survivals. In general, the more abnormal the STT the shorter the fibrinogen survival. The anabolic phase of the curve was also abnormal in that there was delay in incorporation of label in these patients.

Platelet and fibrinogen kinetics in the chronic myeloproliferative disorders

Simultaneous platelet and fibrinogen survival kinetic studies utilizing 75Seselenomethionine was performed on six patients with chronic myelogenous leukemia (CML), four with polycythemia vera (PV), one with idiopathic thrombocytosis (IT), and seven with myelofibrosis and myeloid metaplasia (MMM). The data revealed that platelet survivals, as well as fibrinogen survivals, were increased in CML as compared to patients with the other myeloproliferative disorders (MPD). Platelet survival was shortened in the patients with MPD as compared to the control patients. Thrombotic episodes were noted in three patients with MPD, while another had recurrent rectal bleeding. In all of these patients, platelet turnover was increased and was the only consistent determinant of hemostatic abnormality. Platelet adhesiveness and aggregation studies were inconsistently altered in any group and were not useful predictors of the risk of hemorrhagic or thrombotic diathesis. The data suggest that the platelets produced by patients with CML are functionally abnormal and underutilized when compared to control patients and to patients with other MPD. The thrombocytosis of CML results from decreased platelet utilization rather than from overproduction. Overutilization of platelets in patients with other MPD contributes to the thrombotic tendency noted in these patients. These results suggest another distinctive feature which separates CML from the other MPD. Platelet and fibrinogen kinetic studies are important in evaluating the pathophysiology of the thrombocytopenia or thrombocytosis of the myeloproliferative diseases as well as in investigating the physiology of hemostasis.

Platelet and Fibrinogen Kinetics with [75Se]-Selenomethionine in Patients with Myeloproliferative Disorders

Summary: Simultaneous platelet and fibrinogen kinetics were determined with a cohort label, [75Se]selenomethionine, in three patients with chronic myelocytic leukaemia (CML), three with subacute myelogenous leukaemia (SML) and three with myelofibrosis with myeloid metaplasia (MF). In the CML group platelet survival was normal to increased (10.5–14.0 days), platelet turnover was essentially within the control range (22 000–51 000 platelets/μ/day), fibrinogen survival was prolonged (11.0–19.0 days) and fibrinogen turnover decreased (0.12–0.32 mg/ml/day). In two patients with MF platelet survival was decreased (5.0–7.5 days) and platelet turnover sharply increased (215 000–385 000 platelet/μl/day): one of these patients had multiple thrombotic episodes with an associated decrease in fibrinogen survival (4.0 days) and increased fibrinogen turnover (0.85 mg/ml/day): the other patient had no haemorrhagic or thrombotic episodes and his fibrinogen survival and turnover were within normal limits. Four patients, three with SML and one with MF, presented with thrombocytopenia. Kinetic studies were performed to aid in selecting those patients that might benefit from splenectomy. Splenectomy was performed in two with excellent results. Platelet and fibrinogen kinetics are important adjuncts to the study of the pathogenesis, differential diagnosis, and therapy of the myeloproliferative disorders.

Fibrinogen Survival with [75Se]Selenomethionine during l‐Asparaginase Therapy

Summary. Fibrinogen anabolism and catabolism in four patients (acute lymphoblastic leukaemia; lymphosarcoma cell leukaemia; generalized lymphosarcoma; hypernephroma) were determined with [75Se]selenomethionine during a period of hypofibrinogenaemia induced by l‐asparaginase. The anabolic phase was normal but the fibrinogen survival decreased to 1.5–4.0 days (normal range, 7.8 ± 2.8 days). Heparin therapy did not affect either the fibrinogen levels or abnormal thrombin times. In two patients with widespread Hodgkins disease in whom l‐asparaginase therapy was started after the labelling of fibrinogen with [75Se]selenomethionine, the fibrinogen survival was normal. The results suggest the production of an intrinsically abnormal fibrinogen with a decreased survival during l‐asparaginase administration.

Platelet and Fibrinogen Kinetics with [75Se]Selenomethionine in Thrombocytopenic States. II

Simultaneous platelet and fibrinogen kinetics were determined with a cohort label, [75Se]selenomethionine, in 19 thrombocytopenic patients divided into three groups. Group 1 consisted of six patients with idiopathic thrombocytopenic purpura, five were splenectomized and one treated with corticosteroids after the isotope study; Group 2 consisted of four patients with hypersplenism who were splenectomized after the isotope study; and Group 3—nonsplenectomized patients—consisted of two with hepatic cirrhosis, six with either leukaemia or lymphoma and one with paroxysmal nocturnal haemoglobinuria (PNH). A control group, consisting of patients with non‐haernatologic disease and normal coagulation profiles, had a mean platelet survival of 10.5 days and a mean fibrinogen survival of 7.8 days. In both Groups 1 and 2 the mean platelet survivals of 2.4 and 5.2 days respectively were sharply decreased as compared to the controls and also to the mean platelet survival of 11.0 days in Group 3. Mean platelet turnovers in all three groups were either decreased or normal as compared to the control range. Platelet survival curves in Groups 1 and 2 suggested random destruction and in Group 3 a combination of random plus senescent destruction. In Groups 1 and 2 splenectomy or corti‐costeroid therapy resulted in excellent haematologic remissions. In all three groups the mean fibrinogen survivals were within the control range of 6.5–9.5 days. However, one patient, in Group 2 had a substantial decrease in both platelet and fibrinogen survival, probably indicative of low‐grade disseminated intravascular coagulation. A hypercoagulable state was not demonstrated in the patient with PNH. Simultaneous platelet and fibrinogen kinetics are important adjuncts to the study of the pathogenesis, differential diagnosis, therapy, and criteria for splenectomy in thrombocytopenic patients.