Ennio C. Rossi

Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia

Prostacyclin production was significantly depressed in foetal and placental vascular tissues from five patients with severe pre-eclampsia in comparison to vascular tissues from women with uncomplicated pregnancy. Such an abnormality may be responsible for a reduced blood flow and defective fetal nutrition thus playing a major role in the pathogenesis of this syndrome.

Sequential Changes in Factor VIII and Platelets Preceding Deep Vein Thrombosis in Patients with Spinal Cord Injury

Summary. The relationships between factor VIII associated activities, platelet function, and venous thrombosis were studied in 18 patients with lower limb paralysis following acute spinal cord injury (SCI). Deep vein thrombosis (DVT) was detected in 13 patients (72%). Eight of the 13 thromboses were documented between 6 and 8 d following injury while the other five episodes were noted on days 11 (two), 13,18 and 22. The detection of thrombosis was preceded by marked increases in VIIIR:Ag and VIII:RCoF whereas VIII:C was only marginally increased. The platelet aggregation response to collagen was hyperactive by the sixth day while the platelet aggregate ratio (PAR) did not become abnormal until after DVT was detected. These studies suggest a chronology in the series of events leading to DVT in patients with lower limb paralysis following SCI. Initial elevations in VIIIR:Ag and VIII:R‐CoF are followed in sequence by increased platelet responsiveness to collagen, the occurrence of DVT, and the appearance of circulating platelet aggregates. Conceivably, VIIIR:Ag elaborated by endothelial cells alters platelet reactivity and provides an important determinant for venous thrombosis.

Deep vein thrombosis in spinal cord injury: effect of prophylaxis with calf compression, aspirin, and dipyridamole.

Deep Vein thrombosis is very common in spinal cord injury patients, and a randomized study comparing the prophylactic use of external pneumatic calf compression, aspirin and dipyridamole has been carried out

Platelet activation in preeclampsia

Platelet activation was assessed in hospitalized third-trimester patients with preeclampsia (n = 11) or chronic hypertension with superimposed preeclampsia (n = 11) and in healthy outpatient pregnant controls (n = 10) by measuring plasma beta-thromboglobulin, platelet factor 4, the platelet aggregate ratio, and the amount of collagen required to produce half-maximal aggregation velocity (Kd). Only plasma beta-thromboglobulin levels differed significantly between patients with preeclampsia (50.1 +/- 37.9; p less than 0.05) or chronic hypertension with superimposed preeclampsia (47.6 +/- 16.3; p less than 0.01) and the control subjects (22.5 +/- 11.3). beta-Thromboglobulin values in patients with preeclampsia, but not chronic hypertension with superimposed preeclampsia, correlated directly with 24-hour urinary protein loss (r = 0.93, p less than 0.001) and serum creatinine levels (r = 0.62, p less than 0.05) and inversely with creatinine clearance (r = 0.60, p = 0.05). We conclude that (1) beta-thromboglobulin is elevated in patients with preeclampsia or chronic hypertension with superimposed preeclampsia, (2) the normal platelet aggregate ratio and the Kd indicate that the increase in beta-thromboglobulin is not due to an intrinsic change in platelet responsiveness, and (3) the elevation of beta-thromboglobulin in patients with either preeclampsia or chronic hypertension with superimposed preeclampsia appears to be secondary to platelet consumption in the microvasculature, although in patients with preeclampsia altered renal function may be contributory.

Sequential changes in coagulation and platelet function following femorotibial bypass

Twenty-four patients who received no antiplatelet medications and underwent femorotibial bypass grafting (nine vein, 12 polytetrafluoroethylene [PTFE], and three composite PTFE-vein) had serial measurements taken of their platelet function and coagulation. The concentration of collagen required to produce half-maximal platelet aggregation (Kd), the platelet aggregation ratio, antithrombin III, factor VIII-related antigen, and fibrinolytic activity (platelet-rich plasma) was measured preoperatively and 3 and 7 days after surgery. Before surgery eight patients exhibited an increase of platelet reactivity to collagen. Following femorotibial bypass grafting, the mean preoperative Kd of 0.52 +/- 0.37 microgram/ml fell to 0.34 +/- 0.35 microgram/ml on the third postoperative day (P less than 0.001) and returned to 0.41 +/- 0.72 microgram/ml on day 7. Factor VIII-related antigen increased from a mean preoperative value of 248 +/- 29% of normal activity to a mean of 360 +/- 96% on postoperative day 3 (p less than 0.01) and further increased to 428 +/- 78% on day 7 (p less than 0.01). Fourteen patients had antithrombin III measurements taken, and their levels also fell on the third postoperative day (110 +/- 5.7% to 71 +/- 6.5%; p less than 0.001). No significant changes in fibrinolytic activity were noted. Persistent platelet reactivity was found in seven patients beyond the seventh postoperative day. After administration of 325 mg of aspirin, the abnormal platelet reactivity ceased. Increased platelet reactivity to collagen, factor VIII-related antigen, and a decrease in the antithrombin III level are indicative of a hypercoagulable state in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The treatment of the hemolytic-uremic syndrome with inhibitors of platelet function

In four patients with clinical and laboratory manifestations of the hemolytic-uremic syndrome, the administration of aspirin and dipyridamole was associated with a dramatic and rapid increase in the platelet count. In three of the four patients there was also improvement in neurologic or renal function. No subject experienced bleeding or other untoward effects. We conclude that a trial of aspirin and dipyridamole therapy is warranted early in the course of the hemolytic-uremic syndrome.

Dose-Related Prolongation of the Bleeding Time by Intravenous Nitroglycerin

The effects of intravenous nitroglycerin (NTG) upon the bleeding time, platelet aggregation response, and plasma 6-keto-PGF1α concentration were measured in 17 patients about to undergo coronary bypass grafting. NTG produced a dose-related prolongation of the bleeding time that correlated with the accompanying decrease in systolic blood pressure. Platelet aggregation was not affected and measurements of 6-keto-PGF1α Failed to reveal detectable levels (< 10 pg/ml) either before or after NTG infusion. This suggests that the prolonged bleeding time associated with NTG infusion may be due to vasodilation and increased venous capacitance, rather than altered vascular-platelet interaction.

A Study of Platelet Retention by Glass Bead Columns (‘Platelet Adhesiveness’ in Normal Subjects)

Summary. Platelet adhesiveness tests using glass bead columns were performed in 54 normal subjects. Native blood was forced through the columns by a syringe pump at a flow rate of 6 ml/min, and effluent blood was collected in four aliquots of 2 ml each. The first two aliquots demonstrated a progressive increase in per cent platelet adhesiveness with maximum adhesiveness achieved in the second aliquot. The third and fourth aliquots showed decreased adhesiveness with a progressive broadening of the range of normal. In 11 of the 54 normal subjects the fourth aliquot of effluent blood contained more platelets than the original whole blood and indicated that platelets previously retained by the column were being returned to the effluent. The per cent platelet adhesiveness in the first aliquot did not vary with the platelet count. However, the absolute number of platelets retained by the column increased as the platelet count increased. Moreover, the number of platelets retained from a given aliquot was directly proportional to the number of platelets retained from previous aliquots. The return of platelets to the effluent in the fourth aliquot was associated with the smallest number of platelets retained from the first three aliquots. Adenosine inhibited the retention of platelets by glass bead columns. Retention of platelets by glass bead columns appears to be determined by platelet adhesion to glass surfaces, platelet to platelet aggregation due to released ADP, and spontaneous platelet disaggregation which becomes evident when the initial number of retained platelets provides an insufficient amount of ADP to sustain aggregation.

The effect of a new non-steroidal anti-inflammatory agent, sulindac, on platelet function

Abstract Sulindac, a new non-steroidal anti-inflammatory agent, was investigated in parallel with ASA and indomethacin for its effects on platelet function. In vitro, in concentrations of 0.28 mM, the drug inhibited collagen-induced platelet aggregation without significantly affecting epinephrine-induced aggregation. ASA, indomethacin, and the sulfide metabolite of sulindac inhibited both collagen and epinephrine-induced aggregation. When all compounds were tested at a concentration of 0.14 mM, only sulindac did not inhibit collagen-induced release of 14 C-serotonin. A randomized, double-blind trial of sulindac, ASA, and placebo demonstrated that inhibition of collagen-induced platelet aggregation by sulindac was transient, disappearing 24 hours after administration of the last dose of the drug. By contrast, inhibition by ASA persisted for more than 24 hours. Similar findings were noted in studies of platelet release of 14 C-serotonin. As compared with the placebo group, the bleeding time was significantly prolonged 6 hours after ingestion of ASA but not after sulindac. Sulindac was clinically well-tolerated, while gastrointestinal complaints were common in subjects taking aspirin. Like ASA, sulindac administration caused no important changes in the clotting time, clot retraction, prothrombin time, partial thromboplastin time, or fibrinogen levels. Thus, in comparison with common anti-inflammatory drugs, sulindac is shown to be a moderate to weak inhibitor of platelet function.

Haemorrhagic Thrombocytopathy Associated with Dilatation of the Platelet—Membrane Complex

We evaluated eight patients from four families because of a history of excessive bleeding. Most patients had prolonged bleeding times, absent secondary wave of platelet aggregation in response to epinephrine, collagen and adenosine diphosphate (ADP), and defective 14C‐serotonin release and platelet factor 3 availability. These findings are characteristic of a platelet release defect. Electron‐microscopic examination of the platelets of seven patients revealed a common abnormality. From 30% to 70% of the platelets in any given sample exhibited a prominent membrane complex and dilated, tortuous surface‐connected canalicular system (‘swiss‐cheese’ platelet). In two patients there was coincident storage‐pool disease, but the remainder had adequate dense bodies and a normal ratio of ATP to ADP. SDS‐polyacrylamide gel electrophoresis of platelet proteins and glycoproteins showed no abnormalities. The patency of the canalicular system was demonstrated in one patient by the observation that dense bodies appeared in the cannaliculi and outside the platelets following collageninduced aggregation of polylysine‐treated platelets. Since platelet‐aggregation responses to the calcium ionophore A23187 were normal, we conclude that the defective platelet function in these patients may be due to impaired calcium mobilization from the morphologically abnormal membrane complex.