Winer Rl

Coagulation cascade, fibrinolytic system, antithrombin III, protein C and protein S in patients maintained on continuous ambulatory peritoneal dialysis.

We studied the coagulation cascade, fibrinolytic system and naturally occurring anticoagulants in a group of 14 patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis (CAPD). The results were compared with those obtained in a group of ten normal volunteers. Plasma procoagulant activities of factors XII, XI, IX, VIII, VII, X and II were significantly greater in the CAPD group as compared to the normal control group. Likewise plasma concentrations of total and free protein S were increased in the CAPD group. Although the mean value for plasma factor V activity in the CAPD group was higher than that found in the control group the difference did not attain statistical significance. In addition plasma fibrinogen concentration and factor VIII-related antigen level were significantly increased in CAPD patients. No significant difference was found between the CAPD patients and the control group with respect to plasma levels of protein C, antithrombin III, plasminogen or alpha 2-antiplasmin. In summary, the results demonstrate a tendency for increased levels of various coagulation factors and protein S in CAPD patients with no significant alterations in the levels of various fibrinolytic and endogenous anticoagulant agents, i.e. antithrombin III and protein C. The clinical significance and the mechanism responsible for the observed changes require further investigation.

Effects of Chronic Spinal Cord Injury and Pressure Ulcer on 25(OH)-Vitamin D Levels

We studied 92 spinal cord injured (SCI) men (50 paraplegics and 42 quadriplegics) with normal renal function, 38 of whom had single or multiple pressure ulcers. The results were compared with those of 28 able-bodied normal controls. Serum concentrations of calcium and magnesium were measured by atomic absorption spectrometry, and 25(OH)-vitamin D was quantitated by a specific competitive binding assay using a sensitive vitamin D binding protein and tritiated 25(OH)-vitamin D. The SCI group exhibited significant reductions in serum 25(OH)-vitamin D and total calcium concentrations as compared to the normal control group. Although the mean serum concentration of 25(OH)-vitamin D in the quadriplegic patients as a whole was lower than that found in the entire paraplegic group, the difference did not attain statistical significance. Similar observations were made when the ulcer-free subgroups of paraplegics and quadriplegics were compared. The SCI subgroup which was least physically active, i.e., those with pressure ulcers, showed the greatest depression of serum 25(OH)-vitamin D, calcium, and magnesium concentrations. The observed reduction in serum 25(OH)-vitamin D in SCI patients appears to be partly related to reduced cutaneous vitamin D biosynthesis from sunlight deprivation occasioned by physical disability and hospitalization. In addition, nutritional deficiency and altered intestinal transport may be involved. The reduction in serum calcium concentration may be related to abnormal vitamin D metabolism and hypoalbuminemia (reduced protein-bound calcium).

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Extrinsic and Common Coagulation Pathways in End-stage Renal Disease Associated with Spinal Cord Injury

Data on the effects of combined long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD) on blood coagulation system are limited. We studied the extrinsic and common pathways of blood coagulation system in 9 men with SCI-ESRD treated with maintenance hemodialysis. Plasma procoagulant activities of factors (F)VII, X and II were measured in a clotting assay using appropriate deficient plasmas as substrate. In addition, the antigen concentration of FII was measured using monospecific antibodies against human FII raised in goat in a gradient plate immunodiffusion system. Also measured were plasma fibrinogen concentration and platelet count. The results were compared with those obtained in a group of 10 ambulatory ESRD patients and 8 normal control volunteers. Plasma coagulant activity of FVII was markedly elevated and plasma fibrinogen concentration was moderately increased in SCI-ESRD patients: In contrast, plasma FII was mildly depressed while platelet count was within normal limits in SCI-ESRD patients. The data indicate that the combination of SCI and ESRD can lead to the alteration of the extrinsic and common coagulation pathways. Further studies are needed to elucidate the precise mechanism and the clinical significance of the observed abnormalities.

Fibronectin and factor XIII in spinal cord injured patients with end-stage renal disease

Fibronectin and factor XIII play a major role in blood coagulation cascade and contribute to wound healing and phagocytic function of macrophages. Spinal cord injured (SCI) patients with end-stage renal disease (ESRD) have been shown to exhibit a variety of coagulation abnormalities, a high incidence of infection and poor healing pressure ulcers. Earlier studies in SCI patients with no discernible renal disease revealed a marked rise in plasma fibronectin in patients with fast healing pressure ulcers. However, no significant rise is found in those with poor healing ulcers. We compared plasma concentrations of fibronectin and factor XIII in a group of 13 SCI-ESRD patients with those of a normal control group. Despite the presence of pressure ulcers, the SCI-ESRD patients as a group failed to show a significant rise in plasma fibronectin concentration. In addition, the mean plasma factor XIII value in the SCI-ESRD group was not significantly different from that of the normal control group. Accordingly, the combination of SCI, ESRD and associated conditions seems to impair the patients ability to mount a rise in plasma fibronectin concentration in response to the presence of pressure ulcers. Failure of SCI-ESRD patients to produce a rise in plasma fibronectin concentration may, in part, account for the poor healing property of pressure ulcers in this population.

Fibrinolytic and Protease Inhibitory Systems in Spinal Cord Injured Patients with End-Stage Renal Disease

Earlier studies have revealed a variety of coagulation abnormalities in patients with long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD). The present study was undertaken to examine the fibrinolytic and protease inhibitory systems in this population. Twelve spinal cord injured men with ESRD were studied. All patients had chronic active urinary tract infections, pressure ulcers and were practically bed-bound. The results were compared with those obtained in a group of 32 normal volunteers. Plasma plasminogen and unstimulated tissue-type plasminogen activator (t-PA) concentrations in the SCI-ESRD group were comparable with those found in the control group. No significant difference was found in plasma plasminogen activator inhibitor (PAI) activity in the two groups. In contrast, plasma alpha 2-antiplasmin antigen concentration and antiplasmin activity were significantly reduced in the study population. In addition, plasma alpha 1-antitrypsin activity and antigen concentration were significantly increased while the alpha 2-macroglobulin activity-to-antigen concentration ratio was significantly reduced in the SCI-ESRD group. Although the mechanism of the observed reduction in alpha 2-antiplasmin and total antiplasmin activity is uncertain, its presence could enhance fibrinolysis in this otherwise thrombosis-prone population. Likewise, elevated alpha 1-antitrypsin could attenuate tissue damage by leukocyte-derived proteases in the face of persistent suppurative infections. The reduced alpha 2-macroglobulin activity-to-antigen concentration ratio was thought to reflect the presence of alpha 2-macroglobulin complexes with various proteases generated by the activation of leukocytes, coagulation, fibrinolytic and other proteolytic systems.