The effect on thrombin generation and anti-Xa levels of thromboprophylaxis dose adjustment in post-cesarean obese patients - A prospective cohort study.

OBJECTIVE: To examine the laboratory anticoagulant effect of two thromboprophylactic low-molecular weight heparin (LMWH) regimens in post-cesarean obese patients. METHODS: A prospective cohort study, performed during 2017-2018 at a university hospital, of post-cesarean obese (>90 kg) patients receiving 40 mg/day (n = 30) or 60 mg/day (n = 30) enoxaparin, and a control group of non-obese (n = 30) post-cesarean patients receiving 40 mg/day enoxaparin. Thrombin generation and anti-Xa were measured twice on the third postoperative day: prior to and 3.5-4 h following the third LMWH dose. RESULTS: Age, parity, weight and body mass index were comparable between the obese study groups. Compared to the control non-obese group, the 40 mg obese and 60 mg obese groups showed increased baseline thrombin generation: medians 491, 581, 571 nM, respectively (P = 0.001 and P = 0.04, respectively). At peak LMWH activity, thrombin generation was higher in the 40 mg than in the 60 mg obese and control groups: medians 2599, 2391, 2229 nM, respectively (P = 0.01 and P < 0.0001, respectively); and thrombin generation was comparable between the 60 mg obese and the control groups (P = 0.58). Similarly, a significantly lower proportion of patients in the 40 mg obese group (10%) had anti-Xa levels within the recommended prophylactic range (0.2-0.5 IU/mL) than in the other groups (P < 0.0001 for both comparisons). CONCLUSION: As determined by thrombin generation and anti-Xa testing, post-cesarean obese patients have an increased procoagulant potential, which was diminished only in those receiving higher dosages of LMWH. These findings support the need for clinical evaluation of LMWH dose adjustment in this setting.

Thromboembolic Events Following Splenectomy: Risk Factors, Prevention, Management and Outcomes.

BACKGROUND: Thromboembolic events following splenectomy are not uncommon. However, the role of thromboprophylaxis and risk factors for thrombosis, as well as the clinical course and outcomes, are not well characterized. METHODS: A retrospective review of individuals who underwent splenectomy between January 2006 and December 2015 in two university hospitals. RESULTS: Overall, 297 patients underwent splenectomy [open splenectomy (n = 199), laparoscopic splenectomy (n = 98)]. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h after surgery until discharge) was provided for all patients. One hundred and sixteen patients (39%) also received an extended thromboprophylaxis course of enoxaparin for 2-4 weeks after discharge. Twenty-three patients (7.7%) experienced thrombotic complications following splenectomy, including 16 cases (5.4%) of portal-splenic mesenteric venous thrombosis (PSMVT), 5 (1.7%) pulmonary embolism and 2 (0.7%) deep vein thrombosis. Longer operative time (mean operative time of 405 vs. 273 min, P = 0.03) was independently associated with PSMVT. Post-splenectomy thrombocytosis was not associated with thrombosis (P = 0.41). The overall thrombosis rate was significantly lower in patients who received an extended thromboprophylaxis course following splenectomy (3.4 vs. 10.5%, P = 0.02). Complete resolution of thrombosis was observed in most cases (n = 20, 87.0%), with no recurrent thrombosis during a mean follow-up of 38 ± 25 months. CONCLUSIONS: Thromboembolic complications, mainly PSMVT, are common following splenectomy. Longer operative time was associated with thrombosis. Significantly lower rates of thrombosis were found in patients who received an extended thromboprophylaxis course.

The inflammatory response of keratinocytes and its modulation by vitamin D: the role of MAPK signaling pathways.

The hormonal form of vitamin D, calcitriol, and its analogs are known for their beneficial effect in the treatment of inflammatory skin disorders. Keratinocytes play a role in epidermal inflammatory responses invoked by breeching of the epidermal barrier, by infectious agents and by infiltrating immune cells. We studied the role of calcitriol in the initiation of keratinocyte inflammatory response by the viral and injury mimic polyinosinic-polycytidylic acid (poly(I:C)) and in its maintenance by tumor-necrosis-factor α (TNFα) and investigated the role of the mitogen-activated protein kinase cascades in these processes and their regulation by calcitriol. The inflammatory response of human HaCaT keratinocytes to poly(I:C) or TNFα was assessed by measuring mRNA levels of 13 inflammation-related molecules by real-time PCR microarray and by in-depth investigation of the regulation of interleukin 8, intercellular-adhesion-molecule 1, and TNFα expression. We found that while calcitriol had only a minor effect on the keratinocyte response to poly(I:C) and a modest effect on the early response (2 h) to TNFα, it markedly attenuated the later response (16-24 h) to TNFα. The expression of CYP27B1, the enzyme responsible for calcitriol production, was marginally increased by poly(I:C) and markedly by TNFα treatment. This pattern suggests that while allowing the initial keratinocyte inflammatory response to proceed, calcitriol contributes to its timely resolution. Using pharmacological inhibitors we found that while the p38 MAPK and the extracellular signal-regulated kinase have only a minor role, c-Jun N-terminal kinase plays a pivotal role in the induction of the pro-inflammatory genes and its modulation by calcitriol.