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Biomedical subjects

S M Rajah

Publications and source records attributed to S M Rajah.

At least 19 recordsLinked to original sources
PubMed1992

Response to heparinization in adults and children undergoing cardiac operations.

The activated clotting time is an unreliable index of anticoagulation status during cardiopulmonary bypass procedures. However, modern instrumentation (Hemotec Hepcon HMS) now allows the monitoring of free heparin levels via automated protamine titration. In the present study, the standard procedure of anticoagulation at Killingbeck Hospital, Leeds, was investigated. Twenty-two pediatric patients and 20 adult patients undergoing open heart procedures involving cardiopulmonary bypass were given empirical doses of heparin (3 mg/kg body weight bolus), and activated clotting time was maintained at a level greater than 450 seconds using the Hemochron Timer. Heparin neutralization was performed at the termination of the bypass period using an empirical equivalent (3 mg/kg) of protamine sulfate. Mean free heparin concentration (+/- standard deviation) fell from 2.26 (+/- 0.45) mg/kg to 1.39 (+/- 0.34) mg/kg over the period 10 to 40 minutes on bypass in children. In adults, free heparin level declined from 2.56 (+/- 0.58) mg/kg to 1.81 (+/- 0.58) mg/kg over the same period. The biological half-life for heparin was 60 minutes in adults and 35 minutes in pediatric patients. Empirical protamine dosing resulted in excess protamine administration when compared with Hepcon titrated dose requirements: for children: median (range), 80 (12 to 350) versus 33 (12 to 97) mg, p less than 0.001; and for adults: 350 (200 to 500) versus 130 (61 to 237) mg, p less than 0.001. In conclusion, empirical heparin administration (3 mg/kg) does not result in "steady-state" anticoagulation during cardiopulmonary bypass, and empirical administration of protamine takes no account of interindividual differences in heparin sensitivity and biological half-life, which may be assessed using the Hepcon HMS.

Adult↗
PubMed1991

Monitoring of coagulation status using thrombelastography during paediatric open heart surgery.

Thrombelastography (TEG) has proved useful in identifying coagulopathies (via assessment of clot elasticity properties) during hepatic surgery, but its role in cardiac surgery has as yet not been defined. Twenty-two children [11M, 11F, mean age (range) 4.9 (0.1-16) years] undergoing open heart surgery were investigated [1] preoperatively, [2] 15 min post protamine, [3] 2 h and [4] 24 h postoperatively using TEG. Comparisons were made between pre- and postoperative measurements and haematological indices. The values obtained from the TEG were: R phase (indicative of thrombokinase and thrombin formation disorders), K phase (indicative of fibrinogenesis) and MA phase (providing information on clot stability and platelet function). The patients were divided into two groups based upon 24 h blood loss; Group 1 - blood loss less than 0.7 ml/kg/h and Group 2 - blood loss greater than 0.7 ml/kg/h. In Group 2 there was a highly significant correlation between post-protamine MA phase and platelet number (r = 0.93, p less than 0.001) but there was no correlation in Group 1 (p greater than 0.1). Furthermore, in Group 2 elevated postoperative blood loss was associated with a prolonged K phase (mean [SD] 12.0 [6.0] versus 6.3 [2.1] min, p less than 0.05) and diminished MA phase (37 [12.5] versus 56 [4.9] mm, p less than 0.01) relative to preoperative values. In Group 1, K and MA phase did not alter significantly (p greater than 0.5 and p greater than 0.2, respectively). TEG predicted with 100% (8/8) accuracy increased post-operative bleeding. The specificity of TEG prediction of future bleeding was 73% [8/11]. Alterations in TEG parameters merit further evaluation as markers of postoperative haemorrhage.

Blood Coagulation↗
PubMed1989

Plasma eicosanoids, platelet function and cold sensitivity.

As abnormal eicosanoid (prostaglandin) metabolism has been suggested as a factor in the aetiology of vasospastic diseases we have measured levels of stable eicosanoid metabolites using a radioimmunoassay in 30 normal subjects and 31 patients with Raynaud's phenomenon. There were 13 patients with primary Raynaud's, ten with Raynaud's secondary to scleroderma and eight men with vibration white finger (VWF) disease. We have also measured platelet aggregation to adenosine diphosphate (ADP), collagen and adrenaline in 19 normal subjects, 22 patients with primary Raynaud's, 12 with Raynaud's secondary to scleroderma and 14 men with VWF. When compared with our normal subjects, patients with VWF have an elevated thromboxane B2 level, with a normal 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) level. Their platelets are less sensitive to ADP and collagen. Patients with primary and secondary Raynaud's have elevated thromboxane B2 levels but this is much more marked in the secondary group. Patients with primary Raynaud's have a normal 6-keto-PGF1 alpha level but in patients with secondary Raynaud's the 6-keto-PGF1 alpha level is markedly raised. The platelets from both groups are more sensitive to ADP and collagen and this is more marked in the secondary group. Whether these phenomena are a cause or an effect of vasospasm remains unknown.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of preclotting on the porosity and thrombogenicity of knitted Dacron grafts.

The effects of single- and four-stage preclotting methods on graft porosity and thrombogenicity were compared in two types of Dacron prosthesis. The single-stage method significantly reduced leakage of blood (P less than 0.001), but did not seal the grafts. The four-stage method rendered the grafts impermeable at the second step. Thrombogenicity was compared by perfusing preclotted grafts with fresh heparinized blood (containing 111In-labelled platelets) in an artificial circulation. Platelet deposition and consumption were significantly less in the four-stage method whilst platelet function remained unchanged during perfusion. We conclude that the four-stage technique is superior to standard preclotting methods by rendering knitted Dacron grafts impermeable and hypothrombogenic.

Blood Coagulation↗
PubMed1988

The effect of indobufen on the thrombogenic potential of a Dacron prosthesis in an artificial circulation.

We have evaluated the effect of indobufen on the potential thrombogenicity of a Dacron vascular prosthesis in an artificial circulation. In a randomised double blind crossover study, ten healthy volunteers received indobufen 200 mg or placebo twice daily for one week. The artificial circulation, incorporating a 15 cm length of 8 mm Dacron graft was perfused for 60 mins with volunteer blood containing autologous 111In labelled platelets. Graft thrombogenicity was assessed by changes in platelet function, isotope labelled platelet studies and scanning electron microscopy. Platelet count fell significantly during graft perfusion (P less than 0.05) and aggregation was significantly inhibited by treatment with indobufen pre perfusion compared with the placebo group (P less than 0.02). While deposition of labelled platelets was not statistically significant, consumption of these platelets was greater in the placebo group (P less than 0.01). Field counts of adherent platelets made from scanning electron micrographs of the indobufen treated group were significantly lower (P less than 0.01) compared with the placebo group. We conclude that indobufen can reduce the thrombogenic potential of Dacron vascular grafts and suggest that it may be an effective antiplatelet agent for use following Dacron bypass surgery.

Blood Vessel Prosthesis↗
PubMed1985

Comparison of the thrombogenicity of four types of knitted Dacron arterial graft in an artificial circulation.

The thrombogenicity of four types of knitted Dacron arterial graft was compared by measuring the effect of each prosthetic graft on human platelet function in an artificial circulation. The grafts examined were plain knitted (Meadox 'Cooley'), knitted double velour (Meadox 'Microvel'), filamentous external velour (U.S.C.I. 'Sauvage Filamentous') and a plain knitted graft with a pyrolytic carbon coating (Meadox 'Carboknit'). Platelet count, adhesion and percentage aggregation were all decreased during perfusion. The greatest changes in these parameters were produced by the filamentous velour graft and the least by the carbon coated graft. Electron microscopy demonstrated significantly more platelets adherent to the filamentous graft (rho less than 0.01) with changes in platelet morphology indicating activation. These results suggest that the filamentous graft is more thrombogenic than the other grafts.

Blood Vessel Prosthesis↗
PubMed1985

Microthrombus formation on hemodialysis membranes: a placebo controlled randomized trail of two doses of Indobufen.

The role of Indobufen in preventing the formation of microthrombi on hemodialysis membranes has been investigated in 18 patients in a placebo controlled randomized double-blind cross-over study. All patients had been on regular maintenance hemodialysis for at least 3 months. Indobufen was given as 100 mg b.d. and 200 mg b.d. each for a 7 day period with a 7 day wash-out period between the treatments. Both Indobufen regimens prevented the fall in platelet count, reduced the increase in plasma BTg levels during dialysis, increased the post dialysis plasma heparin levels (p less than 0.05) and inhibited pre-dialysis platelet aggregation with collagen (p less than 0.05), when compared with placebo treatment. Scanning electron microscopy demonstrated minimal fibrin and reduced platelet deposition following Indobufen treatment. There was no difference in the effect of 100 mg b.d. and 200 mg b.d. Indobufen doses. The drug was well tolerated, despite the relatively high levels measured, only one patient withdrew because of side effects. This study indicates that Indobufen when added to a routine hemodialysis treatment schedule, can significantly reduce platelet activation and the thrombus formation on the hemodialysis membranes.

Blood Platelets↗
PubMed1985

Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts. A double-blind, placebo-controlled, randomized trial.

A total of 125 patients undergoing aorta-coronary bypass grafting for disabling angina were randomized to receive either 330 mg of acetylsalicylic acid (aspirin) plus 75 mg of dipyridamole three times daily or a placebo for 6 months postoperatively. In addition, all patients were given warfarin for 3 months. Repeat angiography was performed at 6 months in 103 patients. In the treatment group 95 grafts were implanted in 48 patients, of which 87 were patent (91.6% patency rate). This figure compares with 88 grafts patent out of 118 implanted in 55 patients in the placebo group (74.6% patency rate) (p less than 0.01). We conclude that antiplatelet therapy improves the early patency of saphenous vein aorta-coronary bypass grafts.

Adult↗
PubMed1981

Arterial graft maturation: the duration of thrombotic activity in Dacron aortobifemoral grafts measured by platelet and fibrinogen kinetics.

Dacron is thrombogenic, hence small arterial grafts of this material frequently thrombose in the period prior to graft maturation. Anti-thrombotic therapy may therefore be indicated to preserve patency during this risk period. To evaluate the thrombogencity of immature Dacron grafts, platelet and fibrinogen kinetics using 51Cr and 125I respectively were measured before operation and at 3, 6 and 9 months in 10 patients following aortobifemoral bypass and in 6 age-matched volunteers. Platelet survival was reduced from 8.8 +/- 0.2 d before surgery to 7.4 +/- 0.24 d at 3 months. This was accompanied by an increase in platelet turnover from 39 +/- 2.4 X 10(9)l-1d-1 to 46.9 +/- 2.9 X 10(9)l-1d-1. Fibrinogen t1/2 fell from 3.72 +/- 0.13 d preoperatively to 3.36 +/- 0.11 d at 3 months, while fibrinogen fractional catabolic rate rose from 0.27 +/- 0.014 to 0.34 +/- 0.014. These changes were all significant (P less than 0.01). Fibrinogen consumption had returned to normal by 6 months following surgery but platelet kinetics only equated to preoperative levels at 9 months. We suggest that Dacron grafts are thrombogenically active for about 9 months. When anti-thrombotic therapy is indicated it should be continued throughout this period.

Aged↗
PubMed1980

Antithrombotic therapy for vascular prosthesis: an experimental model testing platelet inhibitory drugs.

Although Dacron vascular grafts are widely used, they are thrombogenic and rapid blood flow maintains patency. When blood flow is suboptimal, antithrombotic therapy may prevent early occlusion. We evaluated the effect of three platelet inhibitory drugs: acetylsalicylic acid (ASA), dipyridamole (DPM), sulphinpyrazone (SPZ), and a combination of ASA plus DPM on platelet adherence to woven Dacron in an artificial circulation. Heparinized blood from 18 volunteers was divided equally for test and control circuits, and to the test each drug was added in therapeutic concentration. The experiment was repeated ex vivo using blood donated by six volunteers after each had taken, separately for 1 week: (1) no drug; (2) ASA, 300 mg, three times a day; (3) DPM, 100 mg, four times a day; (4) SPZ, 200 mg, four times a day; (5) ASA, 300 mg, plus DPM, 75 mg, combined, three times a day. Platelet count, adhesion and aggregation were measured during the 60-minute perfusion, and scanning electron miscroscopy of the graft's luminal surface was performed. ASA was the most effective single agent, significantly impairing platelet function and reducing consumption of platelets by the graft. DPM reduced platelet adherence only in the ex vivo experiment, and its addition to ASA imparted no further influence. Sulphinpyrazone had little effect in either experiment. Antithrombotic therapy with ASA and DPM requires clinical evaluation.

Aspirin↗
PubMed1979

The interaction of varying doses of dipyridamole and acetyl salicylic acid on the inhibition of platelet functions and their effect on bleeding time.

1 In normal volunteers maximum reductions in platelet functions, collagen aggregation, adhesion and PF4 availability, were achieved using combined doses of 50 mg three times daily dipyridamole + 180 mg ASA or 75 mg three times daily dipyridamole + 120 mg ASA daily. 2 These doses did not prolong the bleeding time. 3 A synergistic effect has been demonstrated with 25 mg dipyridamole three times daily and 60 mg ASA. 4 At higher doses the effects on platelet functions were additive up to the maximal response. 5 The effect of low doses of ASA on platelet function was cumulative. 6 As lower doses of ASA in the combination studied inhibit platelet functions maximally without altering the bleeding time and probably without inhibiting prostacyclin, we suggest that these combinations of dipyridamole and ASA merit consideration in future clinical trials.

Adult↗
PubMed1979

Effect of intrauterine contraceptive device on uterine haemostasis: a morphological study.

The effect of the intrauterine contraceptive device (IUCD) on uterine haemostasis was studied at various stages of the menstrual cycle in a series of 46 patients by light- and electron-microscopy and by following the distribution of an infusion of 51Cr-labelled autologous platelets. The endometrium in contact with the IUCD in the majority of cases showed grooving with atrophy and mild chronic inflammation in the surrounding tissues. The adjacent stroma also showed increased vascularity and occasional foci of haemorrhage but the increased blood loss associated with the presence of the IUCD could not be attributed to mechanical erosion or stromal blood vessels by the device. During menstruation the presence of an IUCD does not appear to inhibit the formation of fibrin/platelet thrombi although both in control and IUCD patients there was a striking paucity of platelet/fibrin thrombi in circumstances where their formation should be enhanced. In contrast to other workers we have not observed that gaps or breaks in the endothelial lining of endometrial blood vessels occur with any greater frequency in patients fitted with an IUCD. The principal mechanism by which uterine haemostasis is achieved remains to be established.

Adult↗