Effect of a Pharmacist-Driven Monitoring Program and Electronic Health Record on Bleeding Log Completeness and Documentation.

BACKGROUND: Pharmacists have the ability to enhance comprehensive care for bleeding disorders patients by bridging the gap between hemophilia treatment centers (HTC) and specialty pharmacies, specifically by monitoring bleeding logs. In September 2015, a pharmacist-driven monitoring program was implemented through the specialty pharmacy associated with a medical center to improve bleeding log completeness and electronic documentation for HTC patients. OBJECTIVE: To measure the effect of a pharmacist-driven bleeding disorder monitoring program on bleeding log completeness, successful bleeding log documentation in the electronic health record (EHR), and pharmacist-driven clinical interventions using an EHR tool. METHODS: A single-group pre-post intervention study was conducted of a pharmacist-driven monitoring program. Pre-implementation (January 1, 2014-December 31, 2014), all patients who received and returned a bleeding log following an appointment at the HTC were included; post-implementation (September 1, 2015-December 30, 2015) included patients seen at the HTC who chose to participate in the program for at least 3 months. Before implementation, patient-completed bleeding logs were scanned into the EHR by clinic staff. After implementation, bleeding logs were completed by a pharmacist and documented using a case management tool in the integrated EHR. Bleeding log records successfully documented in the EHR were collected. Completeness was calculated based on 10 clinical data elements for each bleeding log record. Pharmacist-driven interventions resulting from the program in the post-implementation period were recorded. RESULTS: In the pre-implementation period, 19 of 117 bleeding log records (16.2%) were documented in the EHR; all 15 (100%) records were documented post-implementation (P < 0.001). Among all clinical data elements across all records, 706 of 1,170 data elements were recorded pre-implementation (60.3%), and 120 of 150 (80.0%) were recorded post-implementation (P < 0.001). Pre-implementation, no logs were 100% complete; post-implementation, only 6.7% of logs were fully complete (P = 0.114). For the 15 bleeding log records documented in the EHR during the post-implementation period, 14 documented pharmacist-driven clinical interventions occurred. The majority of interventions fell under coordination of care (8 [57.1%]). CONCLUSIONS: Improvement in bleeding log completeness and documentation in the EHR was associated with the use of an EHR tool and pharmacist-driven monitoring program. DISCLOSURES: Not outside funding supported this study. The authors have nothing to disclose.

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K.

INTRODUCTION: Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. METHODS: Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. RESULTS: In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. CONCLUSION: Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

[Metabolomic study of the action mechanism of nourishing blood effect of fo-shou-san on blood deficiency mice].

The metabolic effect of Fo-Shou-San on blood deficiency mice was studied by using metabolomic method. UPLC-QTOF/MS was used to analyze the plasma metabolome in blood deficiency mice. MS data were processed by MarkerLynx software. With multivariate statistical analysis of plasma metabolite profiles, a clear separation among control, blood deficiency model, and Fo-Shou-San groups was achieved. Potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. The metabolic network of blood deficiency was predicted via MetPA database. Twenty-two potential biomarkers were identified and used to explain the thiamine metabolism, arachidonic acid metabolism, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, nicotinate and nicotinamide metabolism, cysteine and methionine metabolism, tryptophan metabolism, starch and sucrose metabolism, tyrosine metabolism and citrate cycle (TCA cycle). Those metabolic pathways were disturbed in blood deficiency mice, but which could be regulated nearly to normal state after Fo-Shou-San administration. In this study, the metabolomics of blood deficiency mice and the action mechanism of nourishing blood effect of Fo-Shou-San were evaluated. The physiological and metabolic state of the organism could be represented comprehensively by using metabolomics. And metabolomics can be used to evaluate the pharmacodynamics and related mechanisms of Chinese medicine and formulae.

[Evaluate activating blood circulation and dissipating blood stasis effect mechanism of foshousan on acute blood stasis rats on basis of metabolomic approach].

Ice water bath and subcutaneous injection of adrenaline were used to establish the acute blood stasis model of rats. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to study the urine metabolic changes of acute blood stasis rats. Potential biomarkers were selected by variable importance projection, and identified on basis of MS information and databases. The metabolic pathways were predicted via MetPA database. To study the effect of Foshousan on endogenous metabolites of acute blood stasis model rats, find potential biomarkers, and explore the effect mechanism of Foshousan on activating blood circulation and dissipating blood stasis. Eleven potential biomarkers were identified with multivariate statistical analysis of urine metabolite profiles, and which also were used to explain the phenylalanine metabolism, tryptophan metabolism and sphingolipid metabolism. Those disturbed metabolic pathways in acute blood stasis rats could be regulated closely to normal state after Foshousan administration. Metabolomics has a bright prospect in the efficacy evaluation and effect mechanism elucidation of the traditional Chinese medicines.

[Comparison of pharmaceutical chemistry difference of effective parts from yin teng gu bi kang prescription in normal rats and rats with acute blood stasis].

OBJECTIVE: To elucidate the material basis of Yin Teng Gu Bi Kang Prescription (YTGBKP) for efficacy of promoting blood circulation by means of comparing the pharmaceutical chemistry difference of effective parts in normal rats and rats with acute blood stasis. METHODS: The pharmaceutical chemistry fingerprints of effective parts under physiological and pathological status (acute blood stasis) were established by HPLC,and the in vitro and in vivo chromatographic peaks were compared and analyzed. RESULTS: Five batches of drug-containing plasma samples had 14 chromatographic peaks under normal physiological status,among which 3 rooted in plasma, 9 existed originally in YTGBKP,2 were metabolites. The compound with retention lime at 12 min was identified as ferulic acid by comparing with reference standard; While under pathological status (acute blood stasis), five batches of the drug-containing plasma samples had 14 chromatographic peaks, among which 3 rooted in plasma, 9 existed originally in YTGBKP, 2 were metabolites. The compounds with retention time at 12 min and 32 min were identified as ferulic acid and icariin respectively by comparing with reference standards. There were 10 common peaks under normal physiological and pathological status (acute bloodl stasis) excluding peaks in blank plasma. The intensity of the common peaks produced under pathological status was stronger than that under normal physiological status significantly; Variance analysis showed that there were significant differences (P < 0.05) in peak areas of 3 peaks. CONCLUSION: Blood stasis has influence on the absorption and metabolism of most ingredients from YTGBKPi; Prototypes and metabolites may be the effective substance on promoting blood circulation.

[Effect of catalpol and puerarin freeze-dried powder on coagulability, hemorheology and no in rats with Qi-deficiency and blood-stasis syndrome].

OBJECTIVE: To study the effect of catalpol and puerarin freeze-dried powder for injection (CPFPI), a new compound traditional Chinese medicine (TCM) preparation, on coagulability, hemorheology and NO in rats with qi-deficiency and blood-stasis syndrome. METHOD: The model of rats with qi-deficiency and blood-stasis syndrome was established by hunger, fatigue, cold-dampness, panic and high fat diet. Coagulation time (CT) was observed by the glass method, and bleeding time (BT) was measured by tail-cutting method. The effects of CPFPI were also evaluated with prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). HCT was measured by the electric tesistance method, hemorheology indicators were observed by auto-hemorheological instrument. The level of NO in blood serum was measured by NO assay kit. RESULT: CPFPI 65.40 mg x kg(-1) significantly prolonged CT, BT, PT, APTT and TT in rats. The viscosity of whole blood and plasma, hematocrit, erythrocyte aggregation and rigidity index, and reduced viscosity of whole blood in 65.40 mg x kg(-1) groups were lower than model group. CPFPI 65.40 mg x kg(-1) can raise the level of NO in blood serum. 32.70 mg x kg(-1) markedly prolonged CT, PT and APTT and decreased whole blood viscosity, erythrocyte aggregation index and whole blood reduction viscosity. CONCLUSION: CPFPI has a significant effect in improving coagulability and hemorheology index and enhancing NO content in blood serum.

[Effects of the effective components group of xiaoshuantongluo formula on rat acute blood stasis model].

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.

Measuring the level of agreement in hematologic and biochemical values between blood sampling sites in leatherback sea turtles (Dermochelys coriacea).

Conservation programs to protect endangered sea turtles are being instituted worldwide. A common practice in these programs is to collect blood to evaluate the health of the turtles. Several different venipuncture sites are used to collect blood from sea turtles for hematologic and biochemistry tests, depending on the species. To date, it is unknown what affect venipuncture site may have on sample results. The purpose of this study was to measure the level of agreement between hematologic and biochemistry values collected from the dorsal cervical sinus and the interdigital vein of leatherback (Dermochelys coriacea) sea turtles. Paired heparinized blood samples were obtained from the dorsal cervical sinus and the interdigital vein of 12 adult female nesting leatherback sea turtles on Keys Beach, St. Kitts, West Indies. Even though the sample population was small, the data for each chemistry were normally distributed, except for creatine kinase (CK). There was no significant difference when comparing biochemistry or hematologic values by venipuncture site, except for CK (P = 0.02). The level of agreement between sampling sites was considered good for albumin, calcium, globulin, glucose, packed cell volume, phosphorus, potassium, sodium, total protein, total solids, uric acid, white blood cell count, and all of the individual white cell types, while the level of agreement for aspartate aminotransferase and CK were considered poor. This information, coupled with the fact that the interdigital vein affords a less-invasive procedure, demonstrates that the interdigital vein is an appropriate location to use when establishing a hematologic and biochemical profile for leatherback sea turtles.

[Proteins influencing the blood coagulation]. / Proteine mit Einfluss auf die Blutgerinnung.

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

The overall hemostasis potential: a laboratory tool for the investigation of global hemostasis.

A simple and rapid global haemostatic assay for determination of the overall hemostasis potential (OHP) in plasma represents a new approach in detecting alterations in the delicate balance between coagulation and fibrinolysis. The assay is based on repeated spectrophotometric registration of the fibrin-aggregation curve in platelet-poor plasma containing small amounts of exogenous thrombin, tissue-type plasminogen activator, and calcium. The overall coagulation potential and overall fibrinolytic potential are supplementary parameters of OHP, providing details of underlying changes in coagulation and/or fibrinolysis. The OHP assay was evaluated in connection with hypercoagulation in normal pregnancy, preeclampsia, some thrombophilias, coronary heart disease, diabetes, stroke, and vascular surgery as well as with hypocoagulability, especially in patients with hemophilia A or B. Preliminary results also indicate the possible usefulness of the assay in monitoring anticoagulant treatments. Large prospective clinical trials are needed before the method can be recommended for routine clinical application.

Prothrombin complex concentrate mitigates diffuse bleeding after cardiopulmonary bypass in a porcine model.

BACKGROUND: Extracorporeal circuit priming and intravascular volume expansion during cardiopulmonary bypass (CPB) may lead to dilutional coagulopathy and excessive diffuse postoperative bleeding. Prothrombin complex concentrate (PCC) containing clotting factors II (FII), VII (FVII), IX (FIX), and X (FX) could be of potential value in correcting dilutional coagulopathy and reducing blood loss. METHODS: Anaesthetized pigs underwent CPB with hypothermia for 2 h at 25°C followed by 1 h of normothermia. Approximately 1 h after CPB, animals randomly received either isotonic saline 1 ml kg⁻¹ or PCC 30 IU kg⁻¹ in a volume of 1 ml kg⁻¹. Diffuse coagulopathic bleeding was assessed as suture hole blood loss from a Gore-Tex patch placed over a full-thickness incision in the left carotid artery. RESULTS: After CPB, levels of FII, FVII, FIX, and FX declined from baseline by 32% to 48%, and PCC fully or partially reversed those deficits. Median suture hole blood loss after administration of saline placebo was 74 ml. PCC reduced suture hole bleeding by a median of 54 ml with a 95% confidence interval of 6-112 ml (P=0.026) compared with saline. PCC, but not saline, normalized skin bleeding time. Peak thrombin generation markedly decreased after CPB, but then returned in PCC-treated animals to a level higher than baseline by 28.7 nM (14.5-41.1 nM; P=0.031). CONCLUSIONS: PCC was effective in correcting dilutional coagulopathy and reducing diffuse bleeding in an in vivo large-animal CPB model. Further research is warranted on PCC as a haemostatic agent in CPB.

Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model.

BACKGROUND: Fluid resuscitation after traumatic injury may necessitate coagulation factor replacement to prevent bleeding complications of dilutional coagulopathy. Recombinant activated factor VII (rFVIIa) is being widely investigated as a hemostatic agent in trauma. Multicomponent therapy with prothrombin complex concentrate (PCC) containing coagulation factors II, VII, IX, and X might offer potential advantages. METHODS: Anesthetized mildly hypothermic normotensive pigs were hemodiluted by substituting 65% to 70% of total blood volume in phases with hydroxyethyl starch and red cells. Thereafter, animals received 12.5 mL . kg isotonic saline placebo, 35 IU . kg PCC, or 180 microg x kg rFVIIa. Immediately afterward, a standardized spleen injury was inflicted, and prothrombin time (PT) and hemostasis were assessed. Thrombin generation was also determined. RESULTS: Hemodilution depleted levels of factors II, VII, IX, and X markedly, prolonged PT and decreased thrombin formation. PCC and rFVIIa both fully normalized the hemodilution-induced lengthening of PT. In PCC recipients, peak thrombin generation was greater by a median of 60.7 nM (confidence interval 56.4-64.9 nM) compared with the rFVIIa group (p = 0.008). After spleen trauma, time to hemostasis was shortened to a median of 35 minutes in animals treated with PCC versus 94 minutes with rFVIIa (p = 0.016). CONCLUSIONS: In a pilot study involving an in vivo large-animal model of spleen trauma, PCC accelerated hemostasis and augmented thrombin generation compared with rFVIIa. Further investigations are warranted on PCC as a hemostatic agent in trauma.

[Anticoagulative effect and antiplatelet aggregation effect of combination of Hirudo and Tabanus on rat model of blood stasis syndrome].

OBJECTIVE: To observe anticoagulative effect and antiplatelet aggregation effect of the combination of Hirudo and Tabanus with different dose-ratio on rat model of blood stasis syndrome. METHODS: The rat model of blood stasis syndrome was established by subcutaneous injection of adrenaline combined with stimulation of icy water. Then prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) contents and inhibition rate of blood platelet aggregation were determined. RESULTS: Platelet aggregation increases, APTT and PT reduced, and FIB contents increased in model control group significantly (P<0.001). Hirudo, Tabanus and the combination of Hirudo and Tabanus had antiplatelet aggregation effect in varying degrees. APTT and PT were prolonged significantly (P<0.05 and P<0.01, respectively) in Hirudo group, Tabanus group and combination groups, especially in the group with dose-ratio of Hirudo to Tabanus being 4:3. FIB contents decreased significantly in combination group with dose-ratio being 3:1 (P<0.05). CONCLUSIONS: The combination groups of Hirudo and Tabanus have better effect of anticoagulation and antiplatelet aggregation than Hirudo group and Tabanus group. While in the four combination groups, the group recommended by classical TCM monograph with dose-ratio of Hirudo to Tabanus being 4:3, has the best anticoagulation effect.

[New oral anticoagulants. Consequences for perioperative coagulation diagnostics and therapy]. / Neue orale Antikoagulanzien. Konsequenzen für die perioperative Gerinnungsdiagnostik und -therapie.

Dabigatranetexilate and rivaroxaban were approved for prevention of thromboembolic events after orthopedic surgery in 2008. Dabigatran is a direct inhibitor of thrombin and rivaroxaban of factor Xa. Inhibition is reversible and the duration of action is predictable. Both drugs considerably influence the global tests of coagulation thus making postoperative coagulation monitoring more difficult. In order to keep the interaction as low as possible blood samples for assessment of the thromboplastin time (PT) and the partial thromboplastin time (PTT) should be taken immediately before the next drug administration. Blood sampling about 2-4 h after drug administration can be performed to check the efficacy of drug action. Non-urgent operations should be started earliest 24 h after the previous drug application. In cases of emergency interventions due to life-threatening bleeding, administration of prothrombin complex concentrate might be a successful treatment option. Specific antidotes are not available.

[Hemoaggregation dynamics in human-operator during percutaneous laser blood irradiation].

The experiment with essentially healthy male subjects no older than 50 involved functional load testing and irradiation by a low-energy helium-neon laser according to the standard therapeutic regimen (0.2 ml/V/ 30 min/10 sessions). Biomedical evaluation of hemoaggregation was made by 30 parameters of a multifunctional diagnostic system characterizing three blood aggregation levels: rheological (biophysical), coagulolytic (biochemical) and system (mathematical). The investigation resulted in delineation of a single-vector hypodynamic transformation of biophysical and biochemical modules, i.e. decrease in the rheological and coagulative potential mediated by a moderate platelets disaggregation (24.6%) and hyperactivation of plasmin proferments in euglobulin fraction (126.76 %). Added sessions of percutaneous laser irradiation of blood were shown to induce a medium imbalance of biophysical and biochemical hemoaggregation. At the same time, low-energy laser did not modulate significantly the general functional state of human operator as the rheological and coagulative protective potential of organism remained reasonably high (88.89 and 87.5 %, respectively).

Screening haemostasis--looking for global assays: the Overall Haemostasis Potential (OHP) method--a possible tool for laboratory investigation of global haemostasis in both hypo- and hypercoagulable conditions.

A broad spectrum of global haemostatic assays has recently been developed and modified in an attempt to overcome the drawbacks of classical screening tests used for evaluation of coagulation and fibrinolysis. The Overall Haemostasis Potential (OHP) assay is one of such assays. The assay is based on repeated spectrophotometric registration of fibrin-aggregation in citrated plasma, to which small amounts of exogenous thrombin, tissue type plasminogen activator and calcium chloride have been added. The area under the fibrin aggregation curve which then develops is calculated and is the laboratory parameter used for OHP determination. The Overall Coagulation Potential (OCP) and Overall Fibrinolytic Potential (OFP) are supplementary parameters of OHP, providing details of underlying changes in coagulation and/or fibrinolysis. The sensitivity of the assay for detecting hypercoagulation in normal pregnancy, in preeclampsia, some thrombophilias, coronary heart disease, diabetes, stroke and vascular surgery has been evaluated. Since the assay can monitor haemostasis balance in the sample, it may serve as a laboratory tool to determine hypocoagulation, especially in patients with haemophilia A or B. Preliminary findings also indicate that the OHP assay may be useful in the monitoring of anticoagulant treatments. Larger controlled clinical studies are, however, mandatory before a definite conclusion about the usefulness of the method can be drawn.

Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin.

Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts. We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation. Seventy warfarin-treated patients with unstable anticoagulation control were randomly assigned in a double-blinded fashion to receive a daily amount of 150 mug oral vitamin K or placebo orally for 6 months. Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it. Vitamin K supplementation resulted in a significantly greater decrease in standard deviation of international normalized ratio (INR) compared with placebo (-0.24 +/- 0.14 vs -0.11 +/- 0.18; P < .001) and a significantly greater increase in percentage time within target INR range (28% +/- 20% vs 15% +/- 20%; P < .01). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled our criteria for having stable control of anticoagulation. However, only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Concomitant supplementation of vitamin K, perhaps through reducing the relative day-to-day variability in dietary vitamin K intake, can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin.

Poor correlation of supratherapeutic international normalised ratio and vitamin K-dependent procoagulant factor levels during warfarin therapy.

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.