Repeated premature hemofilter clotting during regional citrate anticoagulation as indicator of heparin induced thrombocytopenia.

PURPOSE: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. MATERIALS AND METHODS: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. RESULTS: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. CONCLUSION: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation.

Comparison of image quality and radiation dose of different pulmonary CTA protocols on a 128-slice CT: high-pitch dual source CT, dual energy CT and conventional spiral CT.

OBJECTIVES: To compare image quality and radiation dose of high-pitch dual-source computed tomography (DSCT), dual energy CT (DECT) and conventional single-source spiral CT (SCT) for pulmonary CT angiography (CTA) on a 128-slice CT system. METHODS: Pulmonary CTA was performed with five protocols: high-pitch DSCT (100 kV), high-pitch DSCT (120 kV), DECT (100/140 kV), SCT (100 kV), and SCT (120 kV). For each protocol, 30 sex, age, and body-mass-index (mean 25.3 kg/m(2)) matched patients were identified. Retrospectively, two observers subjectively assessed image quality, measured CT attenuation (HU±SD) at seven central and peripheral levels, and calculated signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation exposure parameters (CTDIvol and DLP) were compared. RESULTS: Subjective image quality was rated good to excellent in >92% (>138/150) with an interobserver agreement of 91.4%. The five protocols did not significantly differ in image quality, neither by subjective, nor by objective measures (SNR, CNR). By contrast, radiation exposure differed between protocols: significant lower radiation was achieved by using high-pitch DSCT at 100 kV (p < 0.01 in all). Radiation exposure of DECT was in between SCT at 100 kV and 120 kV. CONCLUSIONS: SCT, high-pitch DSCT, and DECT protocols techniques result in similar subjective and objective image quality, but radiation exposure was significantly lower with high-pitch DSCT at 100 kV. KEY POINTS: New CT protocols show promising results in pulmonary embolism assessment. High-pitch dual-source CT (DSCT) at 100 kV provides radiation dose savings for pulmonary CTA. High-pitch DSCT at 100 kV maintains diagnostic image quality for pulmonary CTA. Dual energy CT uses more radiation but also provides lung perfusion evaluation. Whether the additional perfusion data is worth the extra radiation remains undetermined.

Lack of association of soluble CD40 ligand with the presence of acute myocardial infarction or ischemic stroke in the emergency department.

BACKGROUND: Soluble CD40 ligand (sCD40L) has been proposed as a new risk marker for cardiovascular diseases; however, its possible role as a diagnostic marker in the emergency department (ED) has not yet been investigated. METHODS: We investigated sCD40L for the diagnosis of acute myocardial infarction or ischemic stroke in 1089 consecutive patients (525 males, 564 females; age, 17-98 years; median, 56 years) in an ED treating mainly adults with medical or neurologic emergencies. We used a research assay from Roche Diagnostics to measure sCD40L in heparinized plasma prepared from routinely drawn blood samples. RESULTS: Intraassay and interassay CVs in our laboratory ranged from 1.6%-4.2% and from 4.4%-4.9%, respectively. A multiple linear regression analysis revealed sCD40L concentration to be significantly associated with C-reactive protein concentration (P = 0.012) and platelet count (P < 0.001). In addition, a subgroup analysis revealed a significant association between smoking and sCD40L concentration (P = 0.006). All other tested variables, including discharge diagnosis, age, sex, and other laboratory variables, showed no significant associations. CONCLUSIONS: In adults presenting to the ED, sCD40L is not useful as a diagnostic marker for acute cardiac, cerebrovascular ischemic, or thromboembolic events.

[Therapeutic hypothermia after cardiopulmonary resuscitation - pro and con]. / Therapeutisches Kühlen nach Reanimation - Pro und Contra.

After successful cardiopulmonary resuscitation (CPR), mild therapeutic hypothermia remains the only intervention with a fair evidence of improving outcomes. Randomized controlled trials reported a clinically important benefit, at least for selected victims of cardiac arrest. Therapeutic cooling was associated with higher rates of survival without severe neurological impairment, by 15 absolute percent as compared to controls. Among those delivering acute and intensive care, three of four remain sceptical or do not use therapeutic hypothermia. Is this reluctance justified?

Molecular characterization of three novel splicing mutations causing factor V deficiency and analysis of the F5 gene splicing pattern.

BACKGROUND: Factor V deficiency is a rare autosomal recessive hemorrhagic disorder, associated with bleeding manifestations of variable severity. In the present study, we investigated the molecular basis of factor V deficiency in three patients, and performed a comprehensive analysis of the factor V gene (F5) splicing pattern. DESIGN AND METHODS: Mutational screening was performed by DNA sequencing. Wild-type and mutant F5 mRNA were expressed by transient transfection in COS-1 cells, followed by reverse-transcriptase polymerase chain reaction and sequencing. Real-time reverse-transcriptase polymerase chain reaction was used to evaluate degradation of mRNA carrying premature termination codons. RESULTS: Mutational screening identified three hitherto unknown splicing mutations (IVS8+6T>C, IVS21+1G>A, and IVS24+1_+4delGTAG). Production of mutant transcripts in COS-1 cells demonstrated that both IVS21+1G>A and IVS24+1_+4delGTAG cause the activation of cryptic donor splice sites, whereas IVS8+6T>C causes exon-8 skipping (F5-Delta 8-mRNA). Interestingly, F5-Delta 8-mRNA was also detected in wild-type transfected samples, human liver, platelets, and HepG2 cells, demonstrating that F5 exon-8 skipping takes place physiologically. Since F5-Delta 8-mRNA bears a premature termination codons, we investigated whether this transcript is subjected to nonsense-mediated mRNA decay degradation. The results confirmed the involvement of nonsense-mediated mRNA decay in the degradation of F5 PTC(+) mRNA. Moreover, a comprehensive analysis of the F5 splicing pattern led to the identification of two in-frame splicing variants resulting from skipping of exons 3 and 5-6. CONCLUSIONS: The functional consequences of three splicing mutations leading to FV deficiency were elucidated. Furthermore, we report the identification of three alternatively spliced F5 transcripts.

Emergency correction of coagulation before major surgery in two elderly patients on oral anticoagulation.

Recommendations for urgent reversal of oral anticoagulation with vitamin K1 antagonists are largely derived from case series employing empirical dosing regimens with vitamin K1 and prothrombin complex concentrates. Data on the use of prothrombin complex concentrates in this indication are scarce in the elderly who are at high risk of both hemorrhagic and thrombotic complications. The two cases presented here describe patients older than 75 years who underwent rapid International Normalized Ratio (INR) reversal with prothrombin complex concentrates for surgical treatment of a bleeding ruptured spleen and for emergency surgery of a dissecting aorta. Both patients had their INRs rapidly corrected to