Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. ----- RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. ----- RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. ----- CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome

His\u2013Purkinje system longitudinal dissociation: From bench to bedside. A case of output-dependent fascicular capture

Introduction: Histological studies reported that the His bundle (HB) is partitioned into narrow cords by collagen running in its long axis, providing the anatomical setting necessary for its longitudinal dissociation. Further confirmations came from the demonstration that direct HB pacing normalizes the QRS axis and duration in subjects with proximal HB lesions causing bundle branch block. However, there is no evidence of the possibility of selective HB partitions pacing destined to the composition of branches and fascicles. Methods and Results: We describe a case of intra-Hisian left bundle branch block in which permanent distal HB pacing corrects left ventricular delay and produces different QRS morphology at different voltage outputs, as an expression of different selective HB compartments recruitment. Conclusion: This case would strengthen the limited data in the literature about HB longitudinal dissociation

Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients

Background. Long-term steroid immunosuppression has been associated with the prothrombotic state observed in renal transplant (RT) patients, in whom both hypercoagulability due to an increase of von Willebrand factor/factor VIII complex, and impaired fibrinolysis due to PAI-1 excess have been demonstrated. Our aim was to investigate the effect of steroid withdrawal on fibrinolytic capacity in a group of RT patients. Methods. The fibrinolytic study was performed in 28 RT patients under stable immunosuppression therapy with cyclosporine, azathioprine, and methylprednisolone; only 12 of these patients could repeat the study 6 months after steroid withdrawal. Euglobulin lysis time (ELT), tissue plasminogen activator activity (t-PA:act) and antigen (t-PA:Ag), PAI-1 activity (PAI-1:act), and antigen (PAI-1:Ag) were assayed on blood samples drawn before and 20 min after the venous occlusion test (VO). Results. An hypofibrinolytic state due to a significant increase in PAI-1 levels was confirmed in RT patients receiving triple immunosuppression therapy. RT patient who stayed off steroids showed a significant shortening of ELT both before (P=0.01) and 20' after VO (P=0.005) at the 6-month control. Moreover, after steroid withdrawal, PAI-1:Ag levels decreased significantly (P=0.002) and normalized; in a similar manner PAI- 1:act levels also showed a significant decrease both before (P=0.001), and after VO (P=0.0001). The prevalence of RT patients with impaired fibrinolytic capacity was as high as 83.3% during steroid treatment, and dropped to 16.7% after steroid withdrawal. Conclusions. Our findings confirm that steroid withdrawal may normalize impaired fibrinolytic capacity in RT patients; this improvement may further contribute to reduce the thrombotic risk associated with renal transplantation

A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss.

Clin Exp Rheumatol. 1997 Sep-Oct;15(5):499-505. A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss. Ruffatti A, Orsini A, Di Lenardo L, Nardelli GB, Patrassi GM, Truscia D, Brigato G, Grella P, Todesco S. SourceChair and Division of Rheumatology, University of Padova, Italy. Abstract OBJECTIVE: In this study the efficacy and safety of calcium heparin administered alone for the prevention of fetal loss related to antiphospholipid antibodies (aPL) were evaluated. METHODS: Fifty-three consecutively ascertained pregnancies were followed in 53 patients who had a history of at least 2 consecutive miscarriages during the first trimester and/or 1 fetal death during the second or third trimesters. In addition, all patients had at least 2 positive aPL tests more than 8 weeks apart before pregnancy, or a positive aPL test at the beginning of pregnancy. They were treated with calcium heparin alone, self-administered subcutaneously 3 times daily at dosages varying between 15,000 and 37,500 units. Treatment was started soon after a sonogram demonstrated a live embryo and was continued throughout pregnancy until the end of puerperium. RESULTS: All pregnancies terminated favourably between the 25th and 40th weeks (mean +/- SD: 36.69 +/- 2.91) with planned caesarean section in 27 cases and vaginal delivery in 26. Delivery was brought forward due to maternal and/or fetal complications in 18 cases (33.96%). Calcium heparin was associated with intravenous immunoglobulin therapy in 2 patients with fetal problems unresponsive to anticoagulant treatment alone. The newborns, 30 females and 25 males, had a mean birth weight of 2,828.3 g +/- 706.5 and a mean Apgar score at 5 minutes of 9.60 +/- 0.68. No malformations were observed. Thirty of the 37 examined placentas (81.08%) showed signs of thrombotic events. Only minor side effects of calcium heparin were observed during treatment. CONCLUSION: Our study suggests that calcium heparin administered alone using the dosages and timing described here is effective in achieving the delivery of viable infants, and that it is well tolerated