Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study

Background Fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC) reverse oral anticoagulants. We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass (CPB). Methods Forty patients [with international normalized ratio (INR) ≥ 2·1] assigned semi‐urgent cardiac surgery were randomized to receive either FFP (n = 20) or PCC (n = 20). Prior to CPB, they received either 2 units of FFP or half of the PCC dose calculated according to body weight, initial INR and target INR (≤ 1·5). After CPB and protamine administration, patients received either another 2 units of FFP or the other half PCC dose. Additional doses were administered if INR was still too high (≥ 1·5). Results Fifteen minutes after CPB, more patients reached INR target with PCC (P = 0·007): 7/16 patients vs. 0/15 patients with FFP; there was no difference 1 h after CPB (6/15 patients with PCC vs. 4/15 patients with FFP reached target). Fifteen minutes after CPB, median INR (range) decreased to 1·6 (1·2–2·2) with PCC vs. 2·3 (1·5–3·5) with FFP; 1 h after CPB both groups reached similar values [1·6 (1·3–2·2) with PCC and 1·7 (1·3–2·7) with FFP]. With PCC, less patients needed additional dose (6/20) than with FFP (20/20) (P < 0·001). Both groups differed significantly on the course of factor II (P = 0·0023) and factor X (P = 0·008) over time. Dilution of coagulation factors was maximal at CPB onset. Safety was good for both groups, with only two related oozing cases with FFP. Conclusion PCC reverses anticoagulation safely, faster and with less bleeding than FFP.     

Pre‐treatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma

To determine whether pre‐treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early‐stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut‐off point values to define progression. Two‐year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2‐year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001).     

Improvements in balloon aortic valvuloplasty: Closure devices for large artery access

Objectives : To prospectively compare the efficacy and procedural safety of the radial versus femoral route for cardiac catheterization during uninterrupted warfarin therapy. Background : The optimal treatment strategy for cardiac catheterization in patients receiving long‐term oral anticoagulation has not been defined. Increasing evidence suggests the feasibility and safety of catheterization without warfarin interruption. However, the relative safety and efficacy of the radial and femoral access in fully anticoagulated patients are unknown. Methods : Fifty‐six consecutive patients on chronic warfarin treatment with international normalized ratio (INR) between 1.8 and 3.5 were randomized to undergo coronary angiography, alone, or followed by percutaneous coronary intervention (PCI), via the femoral (n = 29) or radial route (n = 27). Procedural success, in‐hospital major adverse cardiac and cerebrovascular events, access‐site, and bleeding complications were recorded. Results : The two groups were well balanced with similar clinical characteristics at baseline. There were no significant differences in preprocedural antiplatelet therapy or in INR levels between the radial and femoral group (2.62 ± 0.7 vs. 2.48 ± 0.6, respectively, P = 0.63). Procedural success was achieved in all femoral patients, whereas one patient in the radial group (3.7%) required crossover to femoral access. Eight patients from the femoral and 10 patients from the radial group successfully underwent PCI. Access‐site complications occurred only in patients who underwent PCI: three (37.5%) in the femoral versus none in the radial group (P = 0.034). Conclusion : The radial access is as efficacious and safe as the femoral route for coronary angiography in fully anticoagulated patients, but is likely to result in fewer access‐site complications in patients who also undergo PCI. © 2010 Wiley‐Liss, Inc.     

Bridging for an isolated subtherapeutic INR: an evaluation of clinical practice patterns, outcomes, and costs from an anticoagulation clinic

No formal recommendations support bridging patients taking warfarin for a subtherapeutic international normalized ratio (INR). This study aimed to: (1) characterize practices at one anticoagulation clinic, (2) evaluate adverse events, and (3) compare cost of bridging versus withholding bridging for subtherapeutic INR. A retrospective chart review of 320 patients having 546 isolated subtherapeutic INR episodes included patients with an INR below their therapeutic range, preceded by two INRs within or above range. Bridged episodes required more frequent follow-up visits to achieve therapeutic INR (2.5 ± 1.0 vs. 2.2 ± 0.6; P = 0.097), but fewer days until the INR returned to therapeutic range (6.8 ± 5.0 vs. 18.9 ± 16.0; P < 0.0001). The strongest predictor of bridging was the magnitude the INR fell below the therapeutic range, where those with a severely-low INR were 30-fold more likely to be bridged (P < 0.0001), and moderately-low INR episodes were 6-fold more likely to be bridged compared with mildly-low INR (P < 0.0001). Those at high thromboembolic risk were more likely to be bridged than at low-risk (OR 3.39 [1.50–7.68]; P = 0.0034). Increasing age reduced the likelihood of being bridged (OR 0.97 [0.95–0.99]; P = 0.0118). Adverse events were infrequent in both the bridged and non-bridged; thrombosis (2.0 vs. 0.7%), major bleeding (2.0 vs. 1.3%), minor bleeding (4.1 vs. 3.1%) and bruising (18.4 vs. 3.6%). Incremental cost difference of bridging was significantly greater for total cost (967.13) and its components, direct medical (967.13) and its components, direct medical (951.32), transportation (2.73) and productivity cost (2.73) and productivity cost (13.08). It is unclear if bridging for an isolated subtherapeutic INR reduces thrombosis risk, but it is associated with higher costs.     

Usefulness of international normalized ratio to predict bleeding complications in patients with end-stage liver disease who undergo cardiac catheterization

Patients with end-stage liver disease frequently require invasive cardiac procedures in preparation for liver transplantation. Because of the impaired hepatic function, these patients often have a prolonged prothrombin time and elevated international normalized ratio (INR). To determine whether an abnormal prothrombin time/INR is predictive of bleeding complications from invasive cardiac procedures, we retrospectively reviewed, for bleeding complications, the databases and case records of our series of patients with advanced cirrhosis who underwent cardiac catheterization. A total of 157 patients underwent isolated right-sided heart catheterization, and 83 underwent left-sided heart catheterization or combined left- and right-sided heart catheterization. The INR ranged from 0.93 to 2.35. No major procedure-related complications occurred. Several patients in each group required a blood transfusion for gastrointestinal bleeding but not for procedure-related bleeding. No significant change was found in the hemoglobin after right-sided or left-sided heart catheterization, and no correlation was found between the preprocedure INR and the change in postprocedure hemoglobin. When comparing patients with a normal (≤1.5) and elevated (>1.5) INR, no significant difference in hemoglobin after the procedure was found in either group. In conclusion, despite an elevated INR, patients with end-stage liver disease can safely undergo invasive cardiac procedures. An elevated INR does not predict catheterization-related bleeding complications in this patient population.     

Impact of Sildenafil Therapy on Pulmonary Arterial Hypertension in Adults with Congenital Heart Disease

Background : It has been demonstrated that sildenafil is effective in patients with pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults with congenital heart disease (CHD) has been less investigated. Objective : In this prospective, open‐label, uncontrolled and multicenter study, 60 patients with PAH related to CHD received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six‐minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the 12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT; the secondary end point included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening (defined as death, transplantation, and rehospitalization for PAH). Drug safety and tolerability were also examined. Results : Oral sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m, P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32 vs. 2.57 ± 1.42, P= 0.0307). Moreover, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also discovered (mean pulmonary artery pressure, P= 0.0002; cardiac index, P < 0.0001; pulmonary vascular resistance, P < 0.0001). Side effects in this study were mild and consistent with reported studies. None of the enrolled patients experienced significant clinical worsening. Conclusions : This study confirmed and extended previous studies. It suggested that oral sildenafil was safe and effective for the treatment of adult patients with CHD‐related PAH.     

Quantitative defect of glycoprotein ib in severe cirrhotic patients

A decrease of platelet agglutination induced by ristocetin has been described in Cirrhotic patients. In order to investigate the relationship of such phenomenon with a putative defect on piatelet membrane glycoprotein Ib, we have studied the quantitative and functional status of Gp Ib in eleven severe alcoholic cirrhotic patients, and the ability of their formalin-fixed platelets to agglutinate in the presence of normal plasma plus ristocetin. Interestingly, we found a significant decrease of immunoreactive GP Ib molecules (9,978 ± 1,534 vs. 17,064 ± 404 molecules per platelet) and ristocetin-dependent binding of vWF (9,113 ± 1,338 vs. 13,992 ± 1,968 molecules per platelet) (P < 0.01) in comparison to the levels found in a control group of healthy subjects. Immunoblotting analysis of platelet lysates confirmed the reduction of GP Ib level in cirrhotic patients, but showed no modification on the precipitation pattern of this glycoprotein. The ristocetin-induced platelet agglutination (light transmission %) was also significantly lower in patients with Cirrhosis (48 ± 7.6 vs. 92 ± 3.6, P < 0.01), and correlated with the binding of normal vWF (r = 0.863, P = 0.0013). Patients with bleeding times longer than 7 min and/or clinical history of bleeding episodes showed the lowest values of platelet agglutination and GP Ib level. In conclusion, our present results indicate that llver cirrhosis is associated with a relevant decrease of functional GP Ib molecules on the platelet surface. This reduction might be related to the prolongation of bleeding time and to the bleeding diathesis observed in cirrhotic patients. © 1994 Wiley-Liss, Inc.     

Therapeutic rather than prophylactic platelet transfusion policy for severe thrombocytopenia during liver transplantation

Abstract

Platelet transfusion (PTx) has been identified as an important risk factor for morbidity and mortality after liver transplantation (LTx). Our aim was to evaluate the safety of therapeutic rather than prophylactic PTx policy in severe thrombocytopenic patients undergoing LTx. Recipients of LTx were divided into two groups: group I (GI) (n?=?76) platelet count (PC)?≥?50?×?10⁹/l and group II (GII) PC?<?50?×?109/l (n?=?76). Platelets were transfused following a thromboelastometry protocol and clinical signs of diffuse bleeding. Both groups were compared regarding hemoglobin (Hb), international normalized ratio (INR), fibrinogen level, blood loss (BL), blood products required, percentage of bloodless surgery, duration of mechanical ventilation, ICU stay, and vascular complications. Each group was further subdivided according to PTx into (GI NPTx and GII NPTx) with no platelet transfusion (NPTx) and (GI PTx and GII PTx) received PTx. These subgroups were further compared for some variables. Base line Hb was significantly higher while INR was significantly lower in GI.75% avoided PTx in GII. Comparisons of BL, packed red blood cells (PRBCs), and cryoprecipitate transfusion were insignificant. Fresh frozen plasma (FFP) transfusion was higher and the percentage of bloodless surgery was lower in GII. In GII, PC increased after start of surgery. Two cases of hepatic artery thrombosis in GI and one in GII were recorded. Recovery of platelets was quicker, and duration of mechanical ventilation and ICU stay was shorter in NPTx patients regardless the base line PC. Cut-off values of PC?30?×?10⁹/l (with sensitivity 73.7% and specificity 78.8%, p?<?0.01), BL of 3750?ml in GI (sensitivity of 75% and specificity of 69%, p?<?0.01) and of 3250?ml in GII (sensitivity of 84.2% and specificity of 87.7% (p?<?0.01)) could indicate the need of PTx. With therapeutic approach, 75% of patients in GII could avoid unnecessary PTx with its hazards without excessive bleeding. PC in GII increased intraoperatively, PTx may lead to delayed recovery of platelets, increased duration of mechanical ventilation and ICU stay. The given cut-off values may help to guide PTx.     

Comparison of Citrate Anticoagulation During Plasma Exchange With Different Replacement Solutions

The aim of our retrospective study was to compare the application of regional citrate anticoagulation and citrate‐related side‐effects in plasma exchange (PE) with different replacement solutions. We included 35 patients treated with PE with regional citrate anticoagulation and divided them into three groups according to the replacement solution used: human albumin (HA) group (40 PE treatments), fresh frozen plasma (FFP) group (86 PE treatments), or a combination of the two (63 PE treatments). The citrate anticoagulation parameters, ionized calcium and metabolic consequences of citrate were compared. The blood flow and citrate infusion rates were similar in all groups. To maintain comparable values of ionized calcium during PE, significantly more calcium was replaced in the combination group (7.6 ± 1.3 vs. 6.2 ± 2.7 mL/h, P < 0.001) and even more in the FFP group (10.8 ± 1.7 vs. 6.2 ± 2.7 mL/h, P < 0.001) as compared to the HA group. The pH increased significantly and comparably in all groups, but the increase in bicarbonate was significantly higher in the FFP group (4.4 ± 3.0 vs. 2.6 ± 2.1 mmol/L, P = 0.01). A short, heparin‐free hemodialysis session was performed after the PE treatment, because of significant metabolic alkalosis (mainly with pH ≥ 7.5), significantly more often in the FFP group (14/86 PE, P < 0.01) as compared to the HA group (0/40), and only rarely in the combination group (2/63). To conclude, when FFP is used as a replacement solution during PE with citrate anticoagulation, significantly more calcium needs to be replaced and the increase in bicarbonate is greater during PE. The additional citrate contained in FFP, combined with frequent PE treatments, often causes significant metabolic alkalosis, which can be efficiently corrected with a short heparin‐free hemodialysis.     

Safety and Convenience of Continuous Warfarin Strategy During the Periprocedural Period in Patients Who Underwent Catheter Ablation of Atrial Fibrillation

Continuous Warfarin Before AF Ablation. Background: We investigated the efficiency and convenience of a continuous warfarinization (CW) strategy during the periprocedural period of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) in comparison with the classic strategy of switching to heparin (SH). Methods and Results: We compared CW (n = 49) and SH (n = 55, 3 days before RFCA) in 104 patients who underwent RFCA of AF (77 males, 55 ± 12 years old, paroxysmal AF: persistent AF = 63:41). During the procedure, the activated clotting time (ACT) was maintained between 350 and 400 seconds, and a requirement of H, postablation INR, and periprocedural complications were compared. Results were as follows: (1) in the CW group, the preprocedural INR (1.85 ± 0.61 vs 1.05 ± 0.12, P < 0.001) and the proportions of INR > 2.0 after RFCA (1st postprocedure day 61.2% vs 5.5%, P < 0.001; 2nd postprocedure day 83.3% vs 21.8%, P < 0.005) were higher, and the heparin requirement was lower (2012 ± 998 U/30 minutes vs 2921 ± 795 U/30 minutes, P < 0.001) than in the SH group. (2) The incidences of hemorrhagic complications (18.2% vs 18.4%, P = NS) or the major bleeding rates (reduced hemoglobin ≥ 4 g/dL, requiring blood transfusion; 3.6% vs 12.2%, P = NS) were not significantly different in the CW group than in the SH group. Conclusion: The periprocedural CW strategy maintains a more stable INR immediately after AF ablation without increasing hemorrhagic complications compared with the classic strategy of SH. Simple CW can replace SH in an experienced laboratory with a low risk of hemopericardium during AF ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 620‐625, June 2010)     

Systemic and pulmonary hemodynamics in patients with non-cirrhotic portal fibrosis (NCPF) is similar to compensated cirrhosis

Background Non-cirrhotic portal fibrosis (NCPF) is an important cause of portal hypertension (PHT) and variceal bleeding, especially in the developing countries. While the hepatic parenchyma and liver functions are normal, the patho-anatomic defect in these patients is pre- and peri-sinusoidal in nature. Aim To study the systemic and pulmonary hemodynamic alterations in patients with NCPF and compare them with compensated cirrhotic patients. Patients and Methods Patients with NCPF (n = 20, mean age 29.3 ± 9.8 year) and matched Child’s A cirrhotic patients (n = 17, age 34.1 ± 9.8 year) who had bled in the past, underwent hemodynamic measurements using a balloon tipped catheter. Results In NCPF patients, the hepatic venous pressure gradient (HVPG) was significantly lower than in the cirrhotic patients (4.9 ± 1.5 mmHg vs. 15.7 ± 4.5 mmHg; P < 0.01). NCPF patients had hyperdynamic circulation and peripheral vasodilatation comparable to cirrhotic patients; cardiac output (8.0 ± 1.2 l/min vs. 8.4 ± 1.9 l/min; P = 0.4), cardiac index (5.4 ± 0.8 l/min/m² vs. 5.5 ± 1.9 l/min/m²; P = 0.86), mean arterial pressure (88.2 ± 14.1 mmHg vs. 89.9 ± 17.3 mmHg; P = 0.73), systemic vascular resistance (852.8 ± 204.3 dynes · s/cm⁵ vs. 854.1 ± 189.9 dynes · s/cm⁵; P = 0.98) and pulmonary vascular resistance (41.6 ± 18.1 dynes · s/cm⁵ vs. 41.3 ± 17.9 dynes · s/cm⁵; P = 0.95) were comparable in the two groups. Conclusions NCPF associated portal hypertension leads to a hyperdynamic state with high cardiac index and low systemic and pulmonary vascular resistance comparable to compensated cirrhosis. These novel observations suggest a primary role of portal hypertension in the development of hyperdynamic state.     

Radial versus femoral approach for same‐day inter‐facility transfer for percutaneous coronary intervention

Background

The use of radial approach for coronary angiography, followed by same‐day inter‐facility transfer for percutaneous coronary intervention (PCI) has not yet been evaluated.

Objectives

We sought to assess the safety and feasibility of using the transradial as compared to the transfemoral approach in patients undergoing diagnostic angiogram with same‐day transfer to a PCI facility.

Methods

Patients that underwent diagnostic coronary angiography between January 2011 and June 2017 in a referring facility, and were transferred for same‐day PCI were included. Patients’ demographics, as well as procedural data and in‐hospital outcome, were collected.

Results

Three hundred fifty‐two participants were included. Of these, 36 (10.2%) patients received transradial access. Patients in the transradial group were older (68 ± 10 vs 62 ± 12 years, P = 0.007), and received a significantly higher total dose of heparin including both, diagnostic and PCI procedures (5935 ± 1865 vs 10029 ± 2771 units, P < 0.001). None of the transradial patients experienced bleeding or access‐related complications. In the transfemoral group, 9 (3%) vascular‐access complications were recorded. Contrast volume was lower for transradial patients (177 ± 47 vs 216 ± 75 mL, P < 0.001). A higher proportion of outpatients were discharged from the PCI‐center the same day after transradial procedures (53% vs 1.3%, P < 0.001).

Conclusions

Transradial access for inter‐facility transfer for PCI after diagnostic angiogram appears safe and feasible, without increasing the risk for ischemic hand complications. Transradial access was associated with fewer bleeding and vascular access‐site complications, and with a higher likelihood for a same‐day discharge home in outpatients.     

Cardiac Functional Reserve is Diminished in Growth Hormone‐Deficient Adults

Various studies have shown that patients with severe growth hormone deficiency (GHD) have diverse changes in left ventricular (LV) size or performance but so far there is no direct indication of cardiac reserve ability to maintain the circulation during peak exercise. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls. Eighteen patients with severe GHD were studied and compared with 18 age‐, sex‐, and body mass index (BMI)‐matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive hemodynamic measurements during maximal cardiopulmonary exercise testing. Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean ± SD: 4.4 ± 1.0 watts (W) vs. 5.2 ± 1.0 W, P= 0.02), despite attaining similar aerobic exercise peaks (VO_{2 max}, GHD: 2390 ± 822 mL/min vs. controls: 2461 ± 872 mL/min, P= 0.80) and similar peak respiratory exchange ratios. The lower peak cardiac power could not be accounted for by peripheral alterations because both groups reached similar peak exercise systemic vascular resistances. Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate: 154 ± 21 bpm vs. 174 ± 11 bpm, P= 0.001) and a lower cardiac pressure‐generating capacity (systolic blood pressure [SBP] 160 ± 25 mmHg vs. 200 ± 15 mmHg, P < 0.0001). Using this robust noninvasive method of assessing functional cardiac pumping capacity we have for the first time shown that patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure‐generating capacity.     

Coronary anatomy and left ventricular ejection fraction in patients with type 2 diabetes admitted for elective coronary angiography

Patients with diabetes mellitus (DM) have more severe coronary artery disease and a two‐ to fourfold higher risk for myocardial infarction and death as compared to patients without DM. In this study, we analyzed coronary anatomy, left ventricular ejection fraction, and cardiac risk factors in patients with DM referred for coronary angiography and compared them with findings in nondiabetic patients. Coronary anatomy was assessed in a total of 6,234 patients and left ventricular ejection fraction in a subset of 4,767 (76.5%) patients. Diabetic patients (n = 641) were older (60.8 ± 9.6 vs. 58.5 ± 10.5 years; P < 0.0001) and had higher rates of hypertension (65% vs. 47%; P < 0.0001). Three‐vessel disease (DM 44.7% vs. no DM 25.4%; P < 0.0001) and reduced left ventricular ejection fraction (DM 58.4% ± 15.2 vs. no DM 63.9% ± 13.2; P < 0.0001) were significantly associated with DM. After adjustment for age and other vascular risk factors, the presence of DM was associated with a higher atherosclerotic burden. We conclude that advanced coronary heart disease and left ventricular dysfunction are highly prevalent in diabetic patients, independent of age and other cardiovascular risk factors. Thus, cardiac assessment in diabetic patients should, in addition to optimal diabetic control, involve screening for left ventricular dysfunction. Cathet Cardiovasc Intervent 2004;62:432–468. © 2004 Wiley‐Liss, Inc.     

Prolonged bleeding time in cirrhotic patients: Relationship to peripheral vasodilation and severity of cirrhosis

Abstract A prolonged bleeding time (>540 s), measured with a Simplate single template device, was found in 0% of 50 patients with chronic hepatitis and 38% of 154 cirrhotic patients. Cirrhotic patients with a prolonged bleeding time (n= 59) had lower platelet counts (P < 0.001) and a longer prothrombin time (P < 0.001) and activated partial thromboplastin time (P < 0.001) compared with cirrhotic patients with a normal bleeding time (n= 95). A weak but significant negative correlation existed between the bleeding time and platelet count in cirrhotic patients (n= 154, r= -0.3668, P < 0.001). Patients with decompensated cirrhosis had a longer bleeding time in comparison to patients with compensated cirrhosis (621±39 vs 478 ± 27 s, respectively, P < 0.01). The prolonged bleeding time was also discovered in 25% of 83 cirrhotic patients with a platelet count >80 × 10⁹/L and a prothrombin time < 17 s (usually taken as safe limits for invasive procedures). Twenty-seven of the 83 cirrhotic patients received a haemodynamic study by Swan-Ganz catheterization. A lower systemic vascular resistance was found in cirrhotic patients with an abnormal bleeding time than in cirrhotic patients with a normal bleeding time (844 ± 57 vs 1171 ± 60 dyne·s·cm^?5, respectively, P < 0.001), whereas both groups had similar hepatic venous pressure gradient (16.2 ± 1.2 vs 18.1 ± 1.4 mmHg, respectively, P > 0.05). There was a significant negative correlation observed between systemic vascular resistance and bleeding time in cirrhotic patients with a platelet count >80 × 10⁹/L and a prothrombin time < 17 s (n= 27, r= -0.63, P < 0.001). These results demonstrate that prolonged bleeding time is common in patients with cirrhosis. Peripheral vasodilation is probably an important factor in addition to platelet counts and the severity of liver disease in determining the bleeding time in cirrhosis.     

The interaction between preoperative platelet count and function and its relationship with postoperative bleeding in cardiac surgery

Platelet function tests (PFTs) before cardiac surgery are predictive of postoperative bleeding and can guide a correct timing of surgery in patients under P₂Y₁₂ inhibitors. Thrombocytopenia affects PFT and may determine postoperative bleeding. The present study aims to investigate the relationship between platelet count and function, and its role in determining postoperative bleeding in cardiac surgery patients pre-treated with P₂Y₁₂ inhibitors. The study includes 589 consecutive cardiac surgery patients, tested before surgery with platelet count and multiple electrode aggregometry (MEA) ADPtest (investigating P₂Y₁₂ receptor platelet reactivity) and TRAPtest (investigating the thrombin-dependent platelet reactivity). Platelet function was linearly associated (P = 0.001) with platelet count at the ADPtest and the TRAPtest, demonstrating a positive association in the whole spectrum of platelet count. The ADPtest (P = 0.001) and platelet count (P = 0.001) were negatively associated with postoperative bleeding, whereas the TRAPtest was not. At a multivariable analysis, the ADPtest (P = 0.026) and platelet count (P = 0.006) remained independent predictors of postoperative bleeding. The platelet transfusion rate was 5.7% in patients with ADPtest ≥30 U and platelet count ≥150 000 cells/µL, 14.3% in patients with ADPtest ≥30 U and platelet count <150 000 cells/µL, 38.9% in patients with ADPtest <30 U and platelet count ≥150 000 cells/µL, and 50% in patients with ADPtest <30 U and platelet count <150 000 cells/µL (P = 0.001).

Platelet function at MEA is dependent on the platelet count not only in the case of thrombocytopenia, but also in the whole range of platelet count; preoperative platelet count and function are determinants of postoperative bleeding, with a larger effect on platelet transfusions attributable to a poor P₂Y₁₂-dependent platelet function.     

Nocturnal Hypertension and Subclinical Cardiac and Carotid Damage: An Updated Review and Meta‐Analysis of Echocardiographic Studies

Evidence on the association of nocturnal hypertension (NH) with subclinical cardiac and vascular damage is scanty. The authors performed a meta‐analysis to provide comprehensive information on this clinically relevant issue. Full articles providing data on subclinical cardiac and carotid damage as assessed by ultrasonographic methods in patients with NH as compared with patients with nocturnal normotension (NN) were considered. A total of 3657 patients (NH=2083, NN=1574) of both sexes were included in seven studies. Left ventricular mass index was higher in individuals with NH than in those with NN (112±4.7 g/m² vs 98±4.8 g/m²; standard mean difference [SMD], 0.54±0.16; confidence interval [CI], 0.23–0.85; P<.01). Similarly, common carotid intima‐media thickness was greater in patients with NH than in those with NN (751±34 μm vs 653±14 μm; SMD, 0.44±0.08; CI, 0.29–0.59; P<.01). The present meta‐analysis shows an association between NH pattern and increased likelihood of cardiac and carotid structural alterations.     

The International Normalized Ratio does not Reflect Bleeding Risk in Esophageal Variceal Hemorrhage

Background/Aims:

The international normalized ratio (INR) has not been validated as a predictor of bleeding risk in cirrhotics. The aim of this study was to determine whether elevation in the INR correlated with risk of esophageal variceal hemorrhage and whether correction of the INR prior to endoscopic therapy affects failure to control bleeding.

Patients and Methods:

Patient records were retrospectively reviewed from January 1, 2000 to December 31, 2010. Cases were cirrhotics admitted to the hospital due to bleeding esophageal varices. Controls were cirrhotics with a history of non-bleeding esophageal varices admitted with ascites or encephalopathy. All variceal bleeders were treated with octreotide, antibiotics, and band ligation. Failure to control bleeding was defined according to the Baveno V criteria.

Results:

We analyzed 74 cases and 74 controls. The mean INR at presentation was lower in those with bleeding varices compared to non-bleeders (1.61 vs 1.74, P = 0.03). Those with bleeding varices had higher serum sodium (136.1 vs 133.8, P = 0.02), lower hemoglobin (9.59 vs 11.0, P < 0.001), and lower total bilirubin (2.47 vs 5.50, P < 0.001). Multivariable logistic regression showed total bilirubin to inversely correlate with bleeding (OR = 0.74). Bleeders received a mean of 1.14 units of fresh frozen plasma (FFP) prior to endoscopy (range 0-11 units). Of the 14 patients (20%) with failure to control bleeding, median INR (1.8 vs 1.5, P = 0.02) and median units of FFP transfused (2 vs 0, P = 0.01) were higher than those with hemostasis after the initial endoscopy.

Conclusions:

The INR reflects liver dysfunction, not bleeding risk. Correction of INR with FFP has little effect on hemostasis.     

Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk

Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high‐risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM‐1, sICAM‐1, MPO, Cathepsin‐D, PDGF‐AA, PDGF‐AB/BB, RANTES (CCL5), tPAI‐1, and NCAM‐1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM‐1 (2.2 × 10⁶ ± 0.8 × 10⁶ pg/mL vs. 3.1 × 10⁶ ± 0.9 × 10⁶ pg/mL, P < 0.0001), Cathepsin‐D (0.5 × 10⁶ ± 0.1 × 10⁶ pg/mL vs. 0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL, P < 0.0001), PDGF‐AA (10556 ± 4033 pg/mL vs. 14173 ± 4631 pg/mL, P = 0.0008), RANTES (0.1 × 10⁶ ± 0.07 × 10⁶ pg/mL vs. 0.2 × 10⁶ ± 0.06 × 10⁶ pg/mL, P < 0.006), and NCAM‐1 (0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL vs. 0.8 × 10⁶ ± 0.1 × 10⁶ pg/mL, P < 0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM‐1 (P < 0.001), PDGF‐AA (P = 0.025), and RANTES (P = 0.048). Low baseline level of BDNF (P = 0.025), sVCAM‐1 (P = 0.025), PDGF‐AA (P = 0.01), t‐PAI‐1 (P = 0.025) and sICAM‐1 (P = 0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling. Am. J. Hematol. 89:47–51, 2014. © 2013 Wiley Periodicals, Inc.     

Clinical phenotype in heterozygote and biallelic Bernard‐Soulier syndrome—A case control study

Bernard‐Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding disorder. To date heterozygous carriers of BSS mutations have not been shown to have bleeding symptoms. We assessed bleeding using a semi‐quantitative questionnaire, platelet parameters, PFA‐100 closure times, ristocetin response, GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers for related mutations and 29 controls. Eight mutations in GP1BA, GP1BB or GP9 were identified including four previously unknown pathogenic mutations. Subjects with BSS reported markedly more mucocutaneous bleeding than controls. Increased bleeding was also observed in heterozygotes. Compared to controls, patients with BSS had lower optical platelet counts (P < 0.001), CD61‐platelet counts (P < 0.001) and higher mean platelet volume (17.7 vs. 7.8 fL, P < 0.001) and ristocetin response and closure times were unmeasurable. Heterozygotes had higher MPV (9.7 fL, P < 0.001) and lower platelet counts (P < 0.001) than controls but response to ristocetin and closure times were normal. The VWF was elevated in both BSS and in heterozygotes (P = 0.005). We conclude that heterozygotes for BSS mutations have lower platelet counts than controls and show a bleeding phenotype albeit much milder than in BSS. Both patients with BSS and heterozygote carriers of pathogenic mutations have raised VWF. Am. J. Hematol. 90:149–155, 2015. © 2014 Wiley Periodicals, Inc.