Pharmacist involvement in clinical assessment and laboratory testing for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare adverse drug reaction. The anti-PF4 antibody assay (ELISA) is utilized to assist in the clinical evaluation of HIT due to its high negative predictability and wide-spread availability. However, it also associated with false positive results. The 4T score can assist in predicting an individual's risk for HIT and the need for further laboratory testing. This was a single-center prospective observational cohort study. Orders for HIT testing were sent via page to a clinical pharmacist to calculate a 4T score. If low risk, the pharmacist contacted the ordering prescriber to recommend discontinuation of laboratory testing. During the study, a clinical support tool was implemented to assist prescribers with ordering HIT tests. The study was divided into a pharmacist intervention group and a control group. A total of 303 pages were received. One hundred nine were missed due to unavailability of the pharmacist at time of page. A pharmacist reviewed 194 pages and intervened on 132. One hundred seven were scored as low risk, 70 as intermediate risk and 9 as high risk. Pharmacist intervention resulted in discontinuing 64 ELISA and 11 serotonin release assay tests. The clinical support tool resulted in a yearly decrease of HIT testing by 27%. Laboratory cost savings totaled $11,000 but did not include avoidance of laboratory technician or drug cost. Pharmacist involvement in the clinical assessment of HIT and the use of a support tool resulted in the reduction of HIT tests in low risk patients.

Using PARP Inhibitors in Advanced Ovarian Cancer.

Poly(ADP-ribose) polymerase (PARP) proteins are used by cells in several DNA repair processes. PARP inhibition can result in preferential death of cancer cells when another mechanism for repairing DNA is defective. Two PARP inhibitors, olaparib and rucaparib, have been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent, BRCA-associated ovarian cancer. More recently, these two and a third PARP inhibitor, niraparib, were approved by the FDA as maintenance therapy following platinum-based chemotherapy for recurrent ovarian cancer. This has caused a paradigm shift in disease management and a challenge for clinicians, who must decide how best to use these agents in individualized treatment. The oral formulation is attractive to patients, but adverse effects such as nausea and fatigue can impact quality of life. As clinicians become comfortable selecting PARP inhibitors and managing associated toxicities, future steps will be to investigate how to safely administer them in combination with other therapies.

Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program.

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% of patients exposed to unfractionated heparin (UFH). We examined the impact of a hospital-wide strategy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs. The Avoid-Heparin Initiative, implemented at a tertiary care hospital in Toronto, Ontario, Canada, since 2006, involved replacing UFH with low-molecular-weight heparin (LMWH) for prophylactic and therapeutic indications. Consecutive cases with suspected HIT from 2003 through 2012 were reviewed. Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-intervention (2003-2005) and the avoid-heparin (2007-2012) phases. The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in the pre-intervention phase to 49.0 per 10 000 admissions in the avoid-heparin phase ( ITALIC! P< .001). The annual rate of patients with a positive HIT assay decreased 63% from 16.5 to 6.1 per 10 000 admissions ( ITALIC! P< .001), adjudicated HIT decreased 79% from 10.7 to 2.2 per 10 000 admissions ( ITALIC! P< .001), and HITT decreased 91% from 4.6 to 0.4 per 10 000 admissions ( ITALIC! P< .001). Hospital HIT-related expenditures decreased by $266 938 per year in the avoid-heparin phase. To the best of our knowledge, this is the first study demonstrating the success and feasibility of a hospital-wide HIT prevention strategy.

When less is more: can we abandon prophylactic platelet transfusion in Dengue fever?

Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion-in the absence of major bleeding-is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice.

Emergency department awareness of heparin-induced thrombocytopenia: how frequently is risk assessment documented in patients with thrombosis?

Evidence-based guidelines recommend that heparin-induced thrombocytopenia (HIT) should be suspected whenever a patient develops thrombosis or thrombocytopenia 5 to 14 days after heparin initiation. The authors determined how frequently emergency department (ED) physicians document HIT risk assessment in patients presenting with thrombosis. Relevant data were extracted from the ED charts of 134 patients with venous or arterial thrombosis. Documentation (ie, notation of positive or negative findings) existed for recent heparin exposure in 7 (5.2%) of 134 charts, recent hospitalization in 33 (24.6%), history of thrombocytopenia in 0 (0%), and history of thrombosis in 62 (45.5%). Of 35 patients administered heparin in the ED, the preheparin platelet count was available for 19 (54.3%) and old records for 5 (14.3%). Thus, HIT risk assessment frequently remains undocumented for ED patients with thrombosis, including those administered heparin. Approaches to increase HIT awareness and facilitate HIT risk assessment and documentation in the ED may be needed.

The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to be determined. The objective is to describe the clinical course and treatment plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a past history of end stage renal disease (ESRD) of unknown etiology was initiated on NHD in February 2005. His clinical and biochemical parameters improved after conversion to NHD. However, excessive bleeding at the vascular access sites complicated his treatments. Clinical investigations revealed development of HIT Alternative therapeutic strategies were attempted to enable our patient to continue NHD: unfractionated heparin, citrated regional anticoagulation, Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific clinical challenge. We speculate that the augmented exposure of heparin coupled with a primed autoimmune response may be responsible for the development of HIT in our patient. Further research is required to elucidate the appropriate clinical monitoring and treatment strategy for this patient.

Role of prostacyclin (epoprostenol) as anticoagulant in continuous renal replacement therapies: efficacy, security and cost analysis.

BACKGROUND: Heparin remains the drug most commonly used for anticoagulation in continuous renal replacement therapies (CRRTs). However, in patients with hypercoagulability, heparin is insufficient or, in cases with an increased risk of bleeding or thrombocytopenia, it may be contraindicated. Epoprostenol, a potent vasodilator, antithrombotic and antiplatelet agent, could be an alternative. PATIENTS AND METHODS: We studied the records of patients treated under continuous venovenous hemodiafiltration in an academic tertiary hospital of 900 beds, between January 2000 and June 2003. Epoprostenol was prescribed to patients with (i) filter hypercoagulability, defined as consumption of 2 or more filters in the last 24 hours; (ii) low platelet count; or (iii) recent severe hemorrhage. RESULTS: Thirty-eight out of 248 (15%) patients who were under CRRT received epoprostenol for more than 72 hours. Epoprostenol was indicated due to filter hypercoagulability in 48%, thrombocytopenia in 68% (7 patients both) and hemorrhage in 3% of cases. The overall time for epoprostenol therapy was 9,749 hours. The mean filter duration previous to epoprostenol was 23 +/- 12 hours and after administering this drug 38.2 +/- 11.9 hours (p = 0.0001). In 6 patients, heparin and epoprostenol were simultaneously administered. The adverse effects were hemorrhage, which presented in 7 patients (18%) and a fall in blood pressure in another 7 (18%), which recovered in the next 24 hour after starting treatment. Cost analysis demonstrates some advantage with epoprostenol in patients with increased tendency to clotting. CONCLUSIONS: Epoprostenol may be safely used to prevent clotting of the extracorporeal circuits, either alone in patients with thrombocytopenia and/or increased risk of bleeding, or in combination with heparin in states of hypercoagulability.

The cost effectiveness of empiric intravenous immunoglobulin for the antepartum treatment of fetal and neonatal alloimmune thrombocytopenia.

OBJECTIVE: The purpose of this study was to compare the cost effectiveness of empiric intravenous immunoglobulin (IVIG) with that of fetal blood sampling-indicated treatment for the antepartum care of fetal and neonatal alloimmune thrombocytopenia. STUDY DESIGN: We developed a decision analysis model to compare the cost effectiveness of 2 strategies for treatment of pregnancies in women with a history of fetal and neonatal alloimmune thrombocytopenia and an at-risk fetus: 1) IVIG and corticosteroids as indicated by fetal platelet levels determined by fetal blood sampling (FBS); and 2) empiric IVIG. In the first strategy, FBS is used to measure fetal platelets at 24 weeks of gestation and repeated 6 weeks later to guide pharmacotherapy. In the second strategy, weekly IVIG is empirically administered from 24 weeks' to 37 weeks' gestation. The main outcome measure was the marginal cost per quality-adjusted life years (QALY) gained. RESULTS: For every 1000 women with a fetus at risk for recurrent alloimmune thrombocytopenia, empiric therapy, compared with FBS-indicated treatment, decreases perinatal deaths from 31.7 to 11.8 while increasing the number of infants with long-term neurologic deficits from 6.1 to 9.6. These health outcomes translate to 382 QALYs gained with empiric therapy and a cost effectiveness ratio of dollar 32,747 per QALY favoring empiric therapy. In the sensitivity analysis, empiric therapy was not cost effective when the rate of perinatal ICH exceeded 28%. CONCLUSION: Empiric IVIG therapy is a cost-effective strategy for the treatment of women at risk for fetal and neonatal alloimmune thrombocytopenia when the rate of perinatal ICH is less than 28%.

Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin-11) for secondary prophylaxis of thrombocytopenia in solid tumor patients receiving chemotherapy.

BACKGROUND: Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy-induced thrombocytopenia have not been compared. METHODS: The authors constructed a decision-analytic model to compare the alternatives of rhIL-11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources. They incorporated the costs of platelet transfusions and adverse events from rhIL-11 into the analysis. Quality-of-life outcomes were not considered. The pharmacoeconomic analysis was based on the criterion of cost minimization from the payer's perspective. RESULTS: The expected cost of the usual care strategy for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20000 microL(-1)) was US dollars 3495 for a 3-week cycle of chemotherapy. The prophylactic rhIL-11 strategy was more expensive, with an expected cost of US dollars 5328 over the same time period. Nonetheless, it was associated with fewer platelet transfusions, avoiding an average of 6.7 U compared with usual care. The savings from avoidance of platelet transfusion and adverse reactions to transfusion from the use of rhIL-11 were not offset by the substantial cost of the pharmaceutical. The greater expected costs from the rhIL-11 strategy were relatively insensitive to the unit price and efficacy of rhIL-11 and the costs of platelet transfusions and monitoring. CONCLUSIONS: From the payer's perspective, rhIL-11 cannot be considered a cost-saving clinical strategy compared with routine platelet transfusions for patients with severe chemotherapy-induced thrombocytopenia.

The frequency of bleeding complications in patients with haematological malignancy following the introduction of a stringent prophylactic platelet transfusion policy.

Indications for platelet transfusion remain controversial and are frequently based on arbitrary numerical criteria. In October 2000, we introduced a stringent prophylactic-platelet transfusion policy < 10 x 109/l for stable patients and < 20 x 10(9)/l in the presence of major bleeding or additional risk factors. A trigger of < 50 x 10(9)/l was introduced for patients undergoing invasive procedures. A prospective analysis was performed measuring the frequency of minor and major bleeding events, morbidity, mortality and duration of pancytopenia. Blood product usage was assessed and health care savings measured. A total of 98 patients were evaluated on 2147 patient study days and 271 bleeding episodes were recorded. Major bleeding occurred on 1.39% (30/2147) of the study days when platelet counts were < 10 x 10(9)/l and 2.3% (50/2147) of the study days when platelet counts were 10-20 x 10(9)/l. In patients with platelets > 20 x 10(9)/l, there were 117 major bleeding episodes observed on 5.4% of the study days. In patients with no identified additional risk factors present, major haemorrhages were recorded in 0.51% (11/2147) of the study days in patients with platelet counts > or = 10 x 10(9)/l . There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 x 10(9)/l was in place (P = < 0.02). Of note, a 16% reduction in red cell transfusions was recorded. These data confirm that the introduction of a transfusion trigger of < 10 x 10(9)/l in the absence of fresh bleeding and sepsis (> 38 degrees C) is safe and has a significant impact on overall hospital transfusion costs.

Successful autologous bone marrow transplant without the use of blood product support.

We describe a successful autologous bone marrow transplant without the use of any blood products. The patient had relapsed large cell lymphoma. He was a Jehovah's Witness and would not accept transfusions of red blood cells or platelets. He enrolled in our Bloodless Medicine and Surgery Program and was maintained on a regimen of erythropoietin, iron, Amicar, and G-CSF throughout the transplant. He tolerated the transplant well and is alive with no evidence of disease 10 months after autografting.

Selection of delivery method in pregnancies complicated by autoimmune thrombocytopenia: a decision analysis.

OBJECTIVE: To compare three common strategies for selecting delivery methods in term pregnancies complicated by immune thrombocytopenia by contrasting their effects on the number of severely thrombocytopenic neonates delivered vaginally and total cesarean rates. METHODS: We used decision analysis to compare three strategies to select delivery method in women with autoimmune thrombocytopenia, funipuncture at term, intrapartum fetal scalp platelet sampling with delivery mode decisions based on platelet count in the first two strategies, and no testing of fetal platelets with delivery mode determined by standard obstetric criteria. We assumed that the goal of each strategy was to minimize the number of severely thrombocytopenic neonates delivered vaginally while maintaining an acceptable cesarean rate. Severe thrombocytopenia was defined as under 50,000 platelets per microL. Probabilities with ranges (used in sensitivity analyses) were derived from the medical literature. RESULTS: Of the two testing strategies, funipuncture was clearly preferable. Funipuncture resulted in zero cases of severely thrombocytopenic neonates delivered vaginally (as did scalp sampling), with a lower overall cesarean rate compared with fetal scalp sampling (36.6% versus 69.1%). Compared with the no-testing strategy, the funipuncture strategy reduced the number of severely thrombocytopenic neonates delivered vaginally (0 versus 82 per 1000) with a modest increase in the cesarean rate (1.9 cesareans to prevent vaginal delivery of one severely thrombocytopenic neonate). CONCLUSION: Fetal scalp sampling should be abandoned in favor of funipuncture when testing for thrombocytopenia.

Routine maternal platelet count: an assessment of a technologically driven screening practice.

Because automated blood cell counters are now widely used in many clinical settings, an assessment of hemoglobin concentration or hematocrit is invariably accompanied by a platelet count. Thus many asymptomatic pregnant women are being screened for thrombocytopenia. The objective of a good screening program is to reduce morbidity and mortality and thereby improve the quality of life; criteria for the evaluation of proposed or ongoing screening programs are well established. However, the screening of pregnant women for thrombocytopenia seems to have been both technologically mandated and passively accepted. Therefore we systematically evaluated the current de facto screening of asymptomatic pregnant patients for thrombocytopenia in the context of well-explained, desirable characteristics for a successful screening program. We conclude that screening for thrombocytopenia in pregnancy fails to meet established criteria, may actually be harmful (by placing unaffected fetuses of thrombocytopenic women, and the women themselves, at risk from invasive procedures), and should therefore be discontinued.

Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass--assessment of the whole blood ecarin clotting time.

The use of recombinant (r) hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor IIa assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin-spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 micrograms/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin-spiked blood samples obtained from 50 healthy blood donors. CV-values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 micrograms/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

[Thrombocytopenia due to heparin therapy. Use of danaparoid (Orgaran), 13 monocentric cases under authorization of temporary prescription (ATU)]. / Thrombopenies sous héparinothérapie. Utilisation du danaparoïde (Orgaran), trieze cas monocentriques sous le régime de l'ATU.

Since September 1994, danaparoid (Orgaran), a heparinoid, has been used in our centre to treat patients with thrombocytopenia occurring during heparin therapy and who need continuing antithrombotic therapy. We carried out a retrospective study using clinical and biological data on the first 13 consecutive patients treated with danaparoid (for 1 to 18 consecutive days). The platelet count returned to normal for ten patients, but one patient died having contracted a severe sepsis and bleeding occurred in one patient with acute renal failure. In the three other cases, the diagnosis of heparin induced thrombocytopenia (HIT) was in retrospect unlikely and the death of these patients was related to severe underlying diseases which were held responsible for thrombocytopenia. We confirm that danaparoid appears to be an effective, well-tolerated substitute for heparin in HIT patients. The French regulation Temporary Authorization for Prescribing Medicines allowed the prompt use of this as yet unmarketed drug and collection of reliable and pertinent data.

Screening primiparous women and newborns for fetal/neonatal alloimmune thrombocytopenia: a prospective comparison of effectiveness and costs. Immune Thrombocytopenia Working Group.

A prospective study was conducted in three maternity wards to compare the medical outcomes and the costs of two screening strategies for the detection of fetal/neonatal alloimmune thrombocytopenia (FMAIT). A total of 2066 primiparas and 6081 newborns were included. Fifty-two primiparous women with HPA-1b phenotype were found, and 45 were followed during pregnancy. Four women developed antibodies, and two fetuses exhibited FMAIT; therefore, the prevalence of anti-HPA-1a was 2 per 1000, and the prevalence of FMAIT 1 per 1000. Forty-eight thrombocytopenic newborns were found out of a total of 5632 blood samples. Five were HPA-1a children whose mothers were HPA-1b. The cost-effectiveness of screening all primiparous women was $45,000 and of screening all newborns is $18,000-per anti-HPA-1a alloimmunization diagnosed. Costs per fetal death or disability averted were $500,000 for the primiparous strategy and $225,000 for the newborn strategy. In conclusion, screening newborns for neonatal alloimmune thrombocytopenia is more cost-effective than screening primiparous women.

A simplified method for large-scale HPA-1a phenotyping for antenatal screening.

A simplified method for large-scale HPA-1a phenotyping of platelets was developed for use in an antenatal screening programme for fetomaternal alloimmune thrombocytopenia (FMAIT). The test was based on the MAIPA assay, which was modified for antigen-typing with a well-characterized anti-HPA-1a reagent. The resulting assay gave reliable results, was inexpensive and allowed testing of large batches using semiautomated equipment.