Seija Peltonen

Thrombophilia and Arteriovenous Fistula Survival in ESRD

BACKGROUND AND OBJECTIVES The role of thrombophilia in failing arteriovenous fistula (AVF) among patients with ESRD undergoing hemodialysis is not established. This study aimed to assess whether AVF primary patency is associated with thrombophilia and coagulation abnormalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This observational study screened 219 patients between 2002 and 2004 for thrombophilia before AVF surgery. Thrombophilia included factor V Leiden and prothrombin G20210A mutations, protein C and antithrombin activities, and protein S. Coagulation abnormalities included high factor VIII:C, homocysteine, fibrinogen, and d-dimer levels; presence of antiphospholipid antibodies; and short thrombin time. We reviewed patient charts for comorbid conditions, AVF maturation and interventions, kidney transplantation, and patient survival (mean follow-up duration, 3.6 [range, 2.3-5.8] years). Primary patency from the AVF placement and functional primary patency from the first AVF cannulation were analyzed with Kaplan-Meier and Cox proportional hazards models. RESULTS Thrombophilia was present in 9% of the patients, and coagulation abnormalities occurred in 77%. One-year primary patency was 68%; 46% of the AVF failures occurred before the initiation of hemodialysis. Female sex (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.7-4.1) and thrombophilia (HR, 2.2; 95% CI, 1.2-4.2) were independent risk factors for loss of primary patency. Thrombophilia mutations or low antithrombin level (HR, 3.8), female sex (HR, 2.5), and diabetes (HR, 1.9) were associated with shortened functional primary patency of AVF. CONCLUSIONS Against the background of frequent coagulation abnormalities, thrombophilia and female sex predispose patients with ESRD to access failure, mostly due to thrombosis or stenosis.

Activation of coagulation and fibrinolysis despite heparinization during successful elective coronary angioplasty

Our aim was to assess whether the vessel wall trauma induced by balloon inflation during successful elective PTCA results in activation of coagulation and fibrinolysis detectable in circulating blood. In the pilot group (10 patients), when blood was collected under heparinization with adequate anti-Factor Xa activity, catheter-induced thrombin generation was not detected and results obtained from local coronary arterial versus systemic samples did not differ. Locally, von Willebrand factor antigen increased from 73.5 +/- 8.8% to 77.8 +/- 13.1% (p < 0.05) at 5 min after PTCA. In the study group with its 21 patients having adequate heparinization fibrinogen decreased when blood was collected from aorta 15 min after PTCA. In 30% of the patients having the largest calculated area of vessel damage, thrombin-antithrombin III (TAT) complex and prothrombin fragments (F1+2) spiked by at least 25% during PTCA. In all patients the mean TAT values did not increase, but F1+2 (from 0.56 +/- 0.36 to 0.63 +/- 0.39 nmol/l, mean +/- SD, p < 0.05) and D-dimer (from 268 +/- 37 to 325 +/- 45 ng/ml, p < 0.05) rose between 15 to 30 min after PTCA. In conclusion, in every third patient thrombin generation occurs after successful elective PTCA, implying a need for a tighter control than heparin provides.

Increased circulating plasminogen activator inhibitor-1 in patients with patent femorodistal venous bypass

Veins used for arterial bypass grafting undergo wall remodeling when exposed to altered flow, which may affect fibrinolytic mechanisms and subsequently the fate of the graft. Our aim was to study the extent of blood coagulation and fibrinolysis activation in 27 patients with patent grafts two years after femoro-distal bypass surgery. The two matched control groups included 10 and 19 conservatively treated patients having similar degree of arterial insufficiency (mean ankle/brachial blood pressure index) as the bypass group pre- and post-operatively, respectively. Plasma samples for coagulation and fibrinolysis activation were determined using ELISA and chromogenic assays. When compared with the control groups circulating tissue-type plasminogen activator antigen, and especially plasminogen activator inhibitor type-1, PAI-1 antigen and activity were significantly increased, the mean increase ranging between 54% and 140% in the bypass group. Thrombin-antithrombin III complex, fibrinogen, and C-reactive protein, did not differ, while triglycerides were elevated in the bypass group. Ten patients in the bypass group were insulin resistant, but this did not explain the differences in the fibrinolytic parameters between the bypassed and control patients. Patients with peripheral vein grafts had upregulation of PAI-1 in their circulation implying reduced fibrinolytic capacity. Increased PAI-1, a risk factor for venous thrombosis, might reflect developing intimal hyperplasia, and it remains to be studied whether upregulation of PAI-1 in venous grafts associates with graft failure.

Treatment of postpartum thrombotic microangiopathy with plasma exchange using cryosupernatant as replacement

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are rare but acknowledged problems of pregnancy and the postpartum period. These diseases together with thrombotic angiopathy are associated with high maternal and fetal mortality and severe long‐term morbidity. We describe four women with postpartum HUS/TTP treated with plasma exchange cryosupernatant fraction of plasma (CFP) as replacement fluid. Anuria or oliguria at the beginning of treatment and thrombocytopenia [thromb‐ (29–68) × 109/L] were common features. Two of the patients developed a prolonged and more difficult clinical condition affecting the central nervous system and the liver and their platelet counts remained low despite the plasma exchange. The renal and hepatic function of all of the patients recovered fully. This small analysis lends weight to early plasma exchange with cryosupernatant as part of the treatment of postpartum HUS/TTP and suggests that persistent thrombocytopenia is a signal of more serious disease.