[Improved stroke prevention in atrial fibrillation: the Stockholm experience of the introduction of NOACs]. / Förbättrad strokeprevention vid förmaksflimmer med NOAK - Erfarenheter från Stockholms Län.

The introduction of NOACs has put a focus on stroke prevention in atrial fibrillation (AF). The number of patients in Stockholm diagnosed with non-valvular AF increased from 41 008 in 2011 to 51 266 in 2017 and their treatment has been markedly improved. Between 2011 and 2017 total oral anticoagulant treatment increased from 51.6% (warfarin) to 77.3% (31% warfarin, 46.3% NOACs) and aspirin decreased from 31.6% to 7.2%. Treatment was especially improved among patients with CHA2DS2-VASc scores ≥2 and elderly high risk patients. We found an excellent persistence with OAC treatment (88% at 1 year and 83% at 2 years). A comparative effectiveness study showed that NOACs were at least as effective and safe as warfarin even among patients ≥80 years or with previous serious bleeds. After a gradual introduction of NOACs with many educational activities apixaban is now the first-line choice for stroke prevention in AF in Stockholm. Swedish guideline goals are fulfilled and outcomes are improved.

[More with atrial fibrillation, anticoagulants since the coming of NOAK ]. / Fler med förmaksflimmer får antikoagulantia sedan NOAK kom.

Since the introduction of NOAC (non-vitamin K antagonist oral anticoagulants) in 2011 as thromboprophylactic treatment for patients with atrial fibrillation, AF, the number of patients with a diagnosis of atrial fibrillation has increased markedly in our health care registers. The proportion of patients treated with warfarin or NOAC has increased from 47 % to 58 % in 2013. The use of acetylsalicylic acid in patients is decreasing rapidly in patients with AF. NOAC are mostly prescribed by specialists and are mainly used in younger patients with lower CHA2DS2-VASc scores and lower risk for renal insufficiency and bleeding.

A fibrinogen concentrate Haemocomplettan (Riastap) or a Factor XIII concentrate Fibrogammin combined with a mini dose of tranexamic acid can reverse the fibrin instability to fibrinolysis induced by thrombin- or FXa-inhibitor.

To assess whether Haemocomplettan(®) (fibrinogen concentrate) or Fibrogammin(®) (Factor XIII concentrate) can be used to manage bleeding complications of antithrombotic treatment, we examined a normal plasma pool spiked with AR-H067637 (thrombin inhibitor) or rivaroxaban (activated factor X-inhibitor), to which one of the concentrates was added. Fibrin network permeability (Ks), images of Scanning Electron Microscopy (SEM) and Clot Lysis Time (CLT) were examined. Both inhibitors increased the Ks levels, which could be fully or partly reversed by Haemocomplettan(®) or Fibrogammin(®) respectively. However, these modified clots with tightened network remained non-resistant to fibrinolysis, shown as unaffected CLT. Tranexamic acid at a very low concentration (0·4 mg/ml) aided the two concentrates to stabilize the clots, where the prolongation of CLT was more pronounced for a lower dose than a higher dose of Haemocomplettan(®) while Fibrogammin(®) brought the greatest delay to CLT out of all additions. These observations were partly supported by SEM images, displaying alterations of fibrin fibre arrangement known to influence fibirinolysis. The in vitro data suggest that Haemocomplettan(®) or Fibrogammin(®) given in combination with a mini dose of tranexamic acid may slow down the natural clearance of fibrin clot by plasmin and thus prevent patients from haemorrhagic complications during antithrombotic therapy.

Practical viewpoints on the diagnosis and management of heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin-platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of o Ther causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT.

The direct thrombin inhibitors (argatroban, bivalirudin and lepirudin) and the indirect Xa-inhibitor (danaparoid) increase fibrin network porosity and thus facilitate fibrinolysis.

The present study aimed to assess whether the fibrin network structure is modified by the direct thrombin-inhibitors lepirudin, argatroban or bivalirudin and by the indirect Xa-inhibitor danaparoid. Using an in vitro assay that imitates the physiological process of coagulation from thrombin generation to fibrin formation, we examined a normal plasma pool spiked with one of the inhibitors. At concentrations considered to be the plasma levels observed during therapy, almost no influence was detected for lepirudin despite clear-cut effects on "clotting time". However, argatroban, bivalirudin and danaparoid increased the fibrin gel permeability (Ks) to a similar extent. At concentrations higher than the "therapeutic" levels, the dose-response curve in the Ks assay became very steep for lepirudin while those were shallow for the others. In parallel with the drug-induced increases of Ks, larger network pores in 3D-microscopic images and significant shortenings in "clot lysis time" induced by addition of rtPA were observed. Recombinant factor VIII (rFVIII) added to danaparoid-treated samples profoundly counteracted the increase of Ks but had only a slight or no effect on the other drugs. Thus, in vitro, argatroban, bivalirudin and danaparoid have comparable anticoagulating effects, rendering the fibrin network more permeable and less resistant to fibrinolysis. For lepirudin, the steep dose-response curve supports previous clinical findings, i.e. this thrombin inhibitor has a narrow therapeutic window. Furthermore, our data suggest that the haemostatic agent, rFVIII, might be effective in treatment of bleeding complications induced by danaparoid.

[Surgery in acute pulmonary embolism can be a life-saving therapeutic alternative. A follow up of surgically treated patients]. / Kirurgi vid akut lungemboli kan vara ett livräddande behandlingsalternativ. En uppföljning av opererade patienter.

Acute pulmonary embolism occurs in about 10,000 people annually in Sweden, in more than 1000 of whom it has a fatal outcome. The clinical presentation may vary considerably, and a large number of patients with pulmonary embolism are still misdiagnosed. Most patients are treated with anticoagulants and some also with thrombolysis. During a 40-year period, 1957-1996, 12 patients underwent emergency pulmonary embolectomy at the Karolinska Hospital in Stockholm, Sweden. Of these, two (17%) died from anoxic brain damage within the first postoperative month. Four patients died 15-21 years after surgery. Six patients who were still alive at follow-up in 2003 were contacted 7-36 years after the embolectomy and were all in good health. In none of them had pulmonary embolism recurred, but two had suffered deep venous thrombosis. We conclude that emergency pulmonary embolectomy can be a lifesaving procedure, with a good long-term prognosis in patients who survive the early perioperative period.

Hyaluronan in the human neonatal lung: association with gestational age and other perinatal factors.

The aim of this study was to determine the influence of gestational age at birth, postnatal age, specific complications and methods of treatment on the lung hyaluronan concentration in infants. Lung samples and clinical records from 117 infants who died 0-228 days (32 weeks) after preterm or term birth were studied. The lung hyaluronan concentration at death was most strongly associated with the gestational age at birth, an association best described by an exponential function with a negative power coefficient. After adjustments for gestational age, the lung hyaluronan concentration also correlated significantly with birth weight, weight at death, the wet-to-dry lung weight ratio and specific staining for hyaluronan in the pleura. Intrauterine infection was also associated with a significantly higher lung hyaluronan concentration.

Anticoagulant treatment in primary health care in Sweden - prevalence, incidence and treatment diagnosis: a retrospective study on electronic patient records in a registered population.

BACKGROUND: The indications for warfarin treatment in primary health care are increasing. An undertreatment with warfarin is reported in the prevention of embolic stroke in patients with chronic atrial fibrillation, and can be suspected for other indications. Information on the prevalence and incidence of diseases treated with warfarin would reveal useful data for audits concerning management of anticoagulant treatment. We aimed to assess warfarin treatment in primary health care with regard to prevalence, incidence, treatment diagnosis and patient characteristics. METHODS: A one-year retrospective study of electronic patient records up to May 2000 in primary health care in Stockholm, Sweden. Five primary health care centres with a registered population of 75 146. Main outcome measures were prevalence, incidence and treatment diagnosis. RESULTS: Five hundred and seven patients, mean age 71.9 years, were on warfarin treatment. The prevalence was 0.67% (age-adjusted 0.75%), and it was significantly higher for men (0.78%) than for women (0.58%) (p = 0.01). In the age group 75-84 years the prevalence was 4.54%. The most prevalent treatment diagnosis was chronic atrial fibrillation (0.28%), which was more predominant for males (p = 0.02), followed by cerebrovascular disease (0.13%) and deep venous thrombosis (0.13%). The yearly incidence of warfarin treatment was 0.17%, with chronic atrial fibrillation as the predominant treatment diagnosis. CONCLUSION: Warfarin treatment in primary health care is prevalent among the elderly. Chronic atrial fibrillation is the main treatment diagnosis. There is a gender difference favouring men in general and chronic atrial fibrillation as the treatment diagnosis.

Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension.

Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin-antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.

A comparison of spiral computed tomography and latex agglutination D-dimer assay in acute pulmonary embolism using pulmonary arteriography as gold standard.

OBJECTIVE: To compare the diagnostic accuracy of contrast medium enhanced spiral computed tomography of the pulmonary arteries (s-CTPA) and a latex agglutination D-dimer assay in patients with suspected acute pulmonary embolism (PE) by using pulmonary arteriography (PA) and clinical follow-up as reference method. DESIGN: Ninety hemodynamically stable patients with symptoms of acute pulmonary embolism were prospectively evaluated with s-CTPA and pulmonary arteriography (PA) within 24 h from admission. Plasma D-dimer levels on admittance were analyzed using a rapid latex agglutination D-dimer assay. The outcome of D-dimer concentrations in plasma below 0.25 and 0.5 mg/l was studied. RESULTS: All PA and s-CTPA investigations were regarded as of acceptable diagnostic quality in a consensus reading. Thirty-three patients had a positive PA (37%). Three patients had false negative and two patients had false positive s-CTPA findings. s-CTPA had 91% sensitivity, 96% specificity, 94% positive predictive value (PPV) and 95% negative predictive value (NPV). The sensitivity and specificity for D-dimer below 0.5 mg/l were 79 and 88%, respectively. The PPV and NPV were 81 and 87%. If a cut-off level of 0.25 mg/l was used the corresponding figures were 91, 65, 63 and 92%. CONCLUSION: s-CTPA has a higher sensitivity and specificity than latex agglutination D-dimer. A cut-off level of 0.25 mg/l can be used as screening method, but s-CTPA must be performed to exclude false positive cases.