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Biomedical subjects

V V Kakkar

Publications and source records attributed to V V Kakkar.

At least 19 recordsLinked to original sources

Evidence for a plasma inhibitor of the heparin accelerated inhibition of factor Xa by antithrombin III.

The ability of heparin fractions of different molecular weight to potentiate the action of antithrombin III against the coagulation factors thrombin and Xa has been examined in purified reaction mixtures and in plasma. Residual thrombin and Xa have been determined by their peptidase activities against the synthetic peptide substrates H-D-Phe-Pip-Arg-pNA and Bz-Ile-Gly-Arg-pNA. High molecular weight heparin fractions were found to have higher anticoagulant activities than low molecular weight heparin when studied with both thrombin and Xa incubation mixtures in purified mixtures and in plasma. The inhibition of thrombin by heparin fractions and antithrombin III was unaffected by other plasma components. However, normal human plasma contained a component that inhibited the heparin and antithrombin III inhibition of Xa particularly when the high molecular weight heparin fraction was used. Experiments using a purified preparation of platelet factor 4 suggested that the platelet-derived heparin-neutralizing protein was not responsible for the inhibition.

Animals

Prophylaxis for postoperative deep-vein thrombosis. Synergistic effect of heparin and dihydroergotamine.

Randomized clinical trials in 300 patients undergoing major abdominal surgery or hip replacement arthroplasty were performed to investigate the efficacy of dihydroergotamine mesylate, heparin calcium, or a combination of dihydroergotamine with heparin in preventing postoperative deep-vein thrombosis (DVT). The diagnosis of DVT was established by an uptake test using fibrinogen labeled with iodine 125; in patients undergoing hip replacement, phlebography was also employed to confirm or refute the presence of isotopic thrombi. The data indicate that the combination of dihydroergotamine and heparin is more effective than heparin or dihydroergotamine alone in preventing DVT.

Abdomen

Radionuclide venography for the demonstration of the proximal deep venous system.

The majority of pulmonary emboli originate in the deep veins of the lower limb. Fatal emboli usually arise from thrombi that have extended into the femoral or iliac veins or lower inferior vena cava. It is often impossible to demonstrate this area, the proximal venous segment, using conventional ascending venography when there is deep venous occlusion. The alternative methods available--retrograde, pertrochanteric and transfemoral venography--are invasive. Radionuclide venography (RNV) has been developed as a less invasive alternative. It has been found to be accurate in the proximal deep venous system when compared with conventional ascending venography, and in the presence of proximal occlusion it gives images unobtainable by other means. The radiation dose is extremely low and a perfusion lung scan is obtained without further injection of isotope. RNV appears to be the best method for monitoring the progress of thrombolytic therapy for major venous occlusion.

Humans

beta-Thromboglobulin, platelet production time and pletelet function in vascular disease.

Plasma beta-thromboglobulin (beta TG) levels were measured in 103 healthy controls and 112 patients suffering from either peripheral vascular disease (PVD), or cerebrovascular disease (CVD) or deep vein thrombosis (DVT). Plasma beta TG was significantly elevated in 46 PVD patients and 24 recent DVT patients compared to controls, but did not differ significantly in 18 chronic DVT and 24 old CVD patients. In addition, heparin neutralizing activity (HNA) and platelet aggregation induced by adenosine diphosphate, 1-epinephrine and thrombin were compared in 33 out of the 46 PVD patients to 33 controls. The mean HNA was significantly shorter in the PVD patients than in controls. The rate and extent of platelet aggregation were increased in PVD patients compared to controls, but the difference was not statistically significant. Platelet production time (PPT) was measured in 20 controls, 35 PVD patients, nine chronic DVT and 12 chronic CVD patients; significantly shorter PPT was only observed in 14 patients with advanced PVD compared to controls, suggesting increased platelet consumption in these patients. All four assays (plasma beta TG, HNA, platelet aggregation and PPT) were performed in 25 patients; no correlation between the four tests was found in these patients suggesting that the tests were measuring various aspects of platelet function. These results suggest that in vivo platelet consumption as well as platelet aggregation and 'release reaction' are presumably enhanced in PVD and recent DVT patients and that plasma beta TG and PPT assays may be better and more specific indicators of in vivo platelet activation than in vitro platelet aggregation test.

Adolescent

A modified non-radioisotope method for measurement of platelet production time.

Platelet production time (PPT), based on the measurement of malondialdehyde (MDA) production prior to and after the intake of acetylsalicylic acid (ASA), was determined in 20 healthy subjects. High MDA levels were produced by stimulating platelet lipid peroxidation with arachidonic acid, resulting in a reliable, sensitive and accurate technique. PPT correlated well with platelet survival time measured by 51Cr autologous labelled platelets when both methods were used simultaneously in the same patients. This modified non-radioisotope method might serve as a useful aid in the diagnosis of platelet disorders, thromboembolic diseases associated with increased platelet consumption and for the evaluation of drugs affecting platelet function.

Aspirin

Radionuclide venography in the management of proximal venous occlusion. A comparison with X-ray contrast venography.

Ascending contrast venography often fails to show the proximal venous system when there is co-existing occlusion of femoral or iliac veins. Retrograde and pertrochanteric venography both have severe limitations in terms of invasiveness and reliability. Radionuclide venography (RNV) is suggested as a less invasive alternative. 100 patients were investigated by both RNV and X-ray contrast venography (XRV). There was a 72% overall correlation between two methods of investigation. The proximal definition of XRV was limited in those cases with femoral obstruction. RNV, however gave progressively better views as imaging became more proximal and this was accentuated in the presence of femoral or iliac occlusion. RNV is simple and easy to perform and less invasive than XRV. The definition at calf level is such that it cannot at this stage replace XRV as the standard diagnostic procedure. However, in patients with proximal occlusions it gives more reliable information than that obtainable by ascending contrast venography.

Constriction, Pathologic

The origin of thrombi in the deep veins of the lower limb: a venographic study.

A series of 952 patients was examined by ascending venography; 812 with clinically diagnosed deep vein thrombosis (DVT) (group 1) and 140 with clinical features suggestive of pulmonary embolism (group 2). Thrombus was demonstrated in 401 (49.4 per cent) of group 1 and in 74 (53 per cent) of group 2 patients. A total of 535 limbs contained thrombus. In 493 (92 per cent) thrombus was present in the calf with either no further clot, or clot in continuity with that in more proximal veins. In the remaining 42 legs (8 per cent) thrombus either originated from multiple discontinuous sites in the legs and pelvis, or in proximal major veins without concomitant calf involvement. The clinical implications of these findings are discussed.

Femoral Vein