Development of a Coagulation Disorders Unit.

Our Coagulation Disorders Unit in Helsinki, Finland, provides 24/7 services for local and national hospitals and colleagues upon requests regarding bleeding and thrombosis diagnostics and management, including follow-up. The unit has a tight connection between the clinic and laboratory, and its maintenance and sharing knowledge and observations have been priorities, already for over 20 years and will continue to be of major importance. The consultation service is provided by phone during daytime and on-call hours, and in written form sent electronically to the consulting stakeholders. Thrombosis and hemostasis-targeted outpatient clinics are also available for the patients referred to the center. Writing local guidance and official guidelines, Nordic, European and international collaboration, and educational activities including social communication are critical elements for the Coagulation Disorders Unit. Alertness to acute coagulation abnormalities, such as occurred during COVID-19 and vaccine-induced thrombosis and thrombocytopenia, and development of strategies to manage cross-disciplinary problems are topics which call upon broad networking. The Nordic community has an ongoing historical meeting, which has been circulating among coagulation centers for the past 56 years. At the European level, the European Association of Haemophilia and Allied Disorders focuses on bleeding disorders and their management, including safety surveillance. The International Society of Thrombosis and Haemostasis offers excellent basic and clinical benchmarks for any Coagulation Disorders Unit. We hope that the description of the development and implementation of our Coagulation Disorders Unit in Helsinki achieves international interest and broadens international collaboration. Finally, we congratulate STH on its great contributions around the globe and for providing a vivid forum to foster the discipline of thrombosis and hemostasis.

Characterisation of healthcare utilisation and cost of haemophilia care in real-life: A 4-year follow-up study in Finland.

INTRODUCTION: Characterisation of outcomes and costs of haemophilia care in common practice settings is essential for evaluation of new treatment options and for developing clinical practices. In Finland, haemophilia care is mostly centralised to University Hospitals, but treatment practices and costs in adult patients have not been systematically evaluated. AIM: This study was designed to characterise healthcare resource utilisation and treatment costs of adult inhibitor-negative haemophilia patients managed in Finnish University Hospitals. METHODS: The study was based on a nationwide cohort, which consists of all adult haemophilia A (HA; n = 120) and B (HB; n = 35) patients treated in University Hospitals from 2012 to 2016. Patient characteristics and data on healthcare utilisation and factor replacement use were collected from medical records. Direct costs of care were evaluated based on wholesale drug prices and healthcare service utilisation with standard unit costs. RESULTS: Most of HA (79%, n = 96) and HB (84%, n = 31) patients received factor replacement therapy. The median annual bleeding rate (ABR) was low, at 0.8 for HA and 0.5 for HB, also among the patients with on-demand therapy. Over 94% (n = 149) of the patients had outpatient visits during the follow-up period. The mean total annual costs of treatment ranged from €2520 to €176,330. The highest individual cost was factor replacement therapy. CONCLUSION: The outcomes of centralising the management of care to University Hospital Treatment Centres show low ABR and lower treatment costs compared with earlier reports from other high-income European populations. Management strategies, including choosing the right therapy between prophylaxis and on-demand, has been successful in Finland.

Changes in hemostasis parameters in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events: a prospective gender-age adjusted cohort study.

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin-antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.

Modularising outpatient care delivery: A mixed methods case study at a Finnish University Hospital.

BACKGROUND: Modularisation is a potential means to develop health care delivery by combining standardisation and customisation. However, little is known about the effects of modularisation on hospital care. The objective was to analyse how modularisation may change and support health care delivery in specialised hospital care. METHODS: A mixed methods case study methodology was applied using both qualitative and quantitative data, including interviews, field notes, documents, service usage data, bed count and personnel resource data. Data from a reference hospital's unit were used to understand the context and development of care delivery in general. RESULTS: The following outcome themes were identified from the interviews: balance between demand and supply; support in shift from inpatient to outpatient care; shorter treatment times and improved management of service production. Modularisation supported the shift from inpatient towards outpatient care. Changes in resource efficiency measures were both positive and negative; the number of patients per personnel decreased, while the number of visits per personnel and the bed utilisation rate increased. CONCLUSIONS: Modularisation may support health care providers in classifying patients and delivering services according to patients' needs. However, as the findings are based on a single university hospital case study, more research is needed.

Personalized ADP-receptor inhibition strategy and outcomes following primary PCI for STEMI (PASTOR study).

BACKGROUND: Adequate antiplatelet therapy in patients with myocardial infarction with ST-elevation (STEMI) is vital in order to avoid ischemic complications. However, especially with the novel potent oral drugs, bleeding is a major concern. We aimed to investigate whether STEMI patients switched to novel ADP receptor inhibitors due to high platelet reactivity (HPR) on clopidogrel have similar outcomes compared to patients with adequate response to clopidogrel. METHODS: A prospective cohort of 175 STEMI patients (mean age 62.3 years) undergoing primary PCI were included in the PASTOR study. Patients were loaded with 600 mg clopidogrel before the index PCI procedure. Bedside VerifyNow P2Y12 platelet function testing was performed the following morning. RESULTS: 46 patients (26.3%) were found to have HPR on clopidogrel (PRU>235) and were switched to novel ADP receptor antagonists. The remaining 129 patients were treated with clopidogrel. The mean duration of dual antiplatelet therapy (DAPT) was 6.7 months. Duration of entire follow-up of patients was approximately 2 years. Major adverse cardiac events (MACE) while patients were on DAPT occurred in 7.0% in the clopidogrel group compared to 8.7% in the novel ADP receptor antagonist group (p=0.70). No differences were observed between groups off-DAPT either. CONCLUSIONS: Following primary PCI for STEMI, patients with adequate response to clopidogrel show similar outcomes compared to patients switched to novel ADP receptor antagonists due to HPR on clopidogrel. Platelet reactivity testing can be used to guide the choice of antiplatelet therapy in patients with STEMI treated by primary PCI.

[Treatment of venous thrombosis in a cancer patient]. / Syöpäpotilaan laskimotukoksen hoito.

One out of five cancer patients develop venous thrombosis, the risk thereof being 4-7-fold in cancer patients compared with the normal population. Venous thromboses in cancer patients are associated with a higher mortality than in other thrombotic patients. Early detection, effective treatment of venous thrombosis along with sufficiently long and appropriately planned post-thrombotic prophylaxis will improve the prognosis. The treatment of venous thrombosis in a cancer patient differs from that in other patients, as prolonged treatment with low molecular weight heparins has been shown to be more effective than other treatments and is likely to be accompanied by favorable effects as regards cancer biology.

Antiplatelet effect of clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions--limited inhibition of the P2Y12 receptor.

INTRODUCTION: Large individual variability in clopidogrel responses has been reported. However, mechanisms of the non-responsiveness are unclear. Our aim was to study the extent of platelet inhibition at the receptor level by in vitro receptor antagonists of P2Y(12) (AR-C69931MX, cangrelor) and P2Y(1) (adenosine 3',5'diphosphate) in aspirin treated patients with coronary artery disease (CAD) prior to and after in vivo clopidogrel. MATERIALS AND METHODS: 51 aspirin-treated (100 mg/day) patients participated. Blood was collected before and after administration of clopidogrel at 300 mg loading dose on day one, followed by 75 mg/d for four days. Aggregation in platelet-rich plasma was assessed. RESULTS: In 20% of patients clopidogrel failed to inhibit platelet responses to ADP. These non-responders had also decreased sensitivity to an in vitro P2Y(12)-receptor antagonist compared with the responders (mean inhibition of aggregation 25 vs. 32%, difference of means 7% (95% CI 2-12%), P<0.02). Moreover, the P2Y(12)-receptor inhibition by in vivo clopidogrel correlated with the inhibition by in vitro ARMX measured prior to administration of clopidogrel. Neither P2Y(1)-receptor activity, thrombin generation while on aspirin nor basal platelet activity associated with clopidogrel responses. CONCLUSIONS: Concomitant aspirin and clopidogrel treatment failed to suppress platelet activity in 20% of patients. Non-responders to clopidogrel had decreased responses also to another ADP receptor antagonist, which suggests that the impaired response occurs at the level of P2Y(12)-receptor.

Polymorphisms of COX-1 and GPVI associate with the antiplatelet effect of aspirin in coronary artery disease patients.

The antiplatelet effect of aspirin varies individually. This study evaluated whether the antiplatelet effect of aspirin associates with polymorphisms in the genes coding for cyclo-oxygenase-1 (COX-1) and several platelet glycoprotein (GP) receptors in patients with stable coronary artery disease (CAD). Blood samples were collected from 101 aspirin-treated (mean 100 mg/d) patients. Compliance to treatment was assessed by plasma salicylate measurement. Platelet functions were assessed by two methods: 1) Response to arachidonic acid (AA, 1.5 mmol/L in aggregometry, and 2) PFA-100, evaluating platelet activation under high shear stress in the presence of collagen and epinephrine (CEPI). Aspirin non-response was defined as: 1) slope steeper than 12%/min in AA-aggregations, and 2) by closure time shorter than 170 s in PFA-100. The methods used detected different individuals as being aspirin non-responders. Five and 21 patients, respectively, were non-responders according to AA-induced aggregation and PFA-100. Increased plasma thromboxane B2 levels correlated with poor aspirin-response measured with both AA-induced aggregations and PFA-100 (P = 0.02 and P = 0.003, respectively). Of the non-responders detected by AA, 3 of 5 (60%) carried the rare G allele for the -A842G polymorphism of COX-1 in contrast to 16 of 96 (17%) responders (P = 0.016). Diabetes was associated with poor response. Aspirin non-response detected by PFA-100 associated with C13254T polymorphism of GP VI and female gender (P = 0.012 and P = 0.019, respectively). Although two patients were possibly non-compliant, this did not effect present conclusions. Evaluation of aspirin efficacy by AA-induced aggregation and PFA-100 detected different individuals, with different genotypic profiles, as being aspirin non-responders.

Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions.

AIM: Our aim was to evaluate the early efficacy and variability of the platelet inhibition exerted by 300 mg clopidogrel for the purpose of acute percutaneous coronary interventions using platelet function tests. METHODS AND RESULTS: Elective percutaneous coronary intervention was used as a timely model in which clopidogrel was added to ongoing acetylsalicylic acid (aspirin) (100 mg/day) at 2.5 h prior to procedure. Blood samples were collected before administration of clopidogrel and immediately before the intervention from 50 patients. Platelet functions were assessed with traditional aggregation and PFA-100. At baseline, 14 (28%) patients were poor responders to aspirin according to PFA and 9 (18%) continued to show arachidonic acid-induced aggregation. After clopidogrel ADP-triggered aggregation was only modestly inhibited in 40% of the patients. Eight percent of the study population was left without any measurable antiplatelet effect. The patients with modest response to clopidogrel had higher levels of c-peptide (1.5 nmol/L) than the ones responding well (0.9 nmol/L, P<0.05). CONCLUSION: Neither ongoing aspirin treatment nor added clopidogrel did reach an expected extent of platelet inhibition. This study shows that aspirin-treated patients undergoing PCI gain highly variable levels of platelet inhibition with short-term clopidogrel 300 mg. At 2 h after adding clopidogrel it failed to enhance platelet inhibition in 40% of the patients. In future, targeted platelet function tests may be helpful to individually select an effective antiplatelet medication for these patients. This study suggests that for acute PTCA clopidogrel does not reach the optimal antithrombotic efficacy in all patients.